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https://www.readbyqxmd.com/read/28637176/dissociation-of-striatal-dopamine-and-tyrosine-hydroxylase-expression-from-aging-related-motor-decline-evidence-from-calorie-restriction-intervention
#1
Michael F Salvatore, Jennifer Terrebonne, Mark A Cantu, Tamara R McInnis, Katy Venable, Parker Kelley, Ella A Kasanga, Brian Latimer, Catherine L Owens, Brandon S Pruett, Yongmei Yu, Robert Luedtke, Michael J Forster, Nathalie Sumien, Donald K Ingram
The escalating increase in retirees living beyond their 8th decade brings increased prevalence of aging-related impairments, including locomotor impairment (Parkinsonism) which may affect ~50% of those reaching age 80, but has no confirmed neurobiological mechanism. Lifestyle strategies that attenuate motor decline, and its allied mechanisms, must be identified. Aging studies report little to moderate loss of striatal dopamine (DA) or tyrosine hydroxylase (TH) in nigrostriatal terminals, in contrast to ~70-80% loss associated with bradykinesia onset in Parkinson's disease...
June 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28637027/phospho-axl-is-widely-expressed-in-glioblastoma-and-associated-with-significant-shorter-overall-survival
#2
Julia Onken, Peter Vajkoczy, Robert Torka, Claudia Hempt, Victor Patsouris, Frank L Heppner, Josefine Radke
Receptor tyrosine kinase AXL (RTK-AXL) is regarded as a suitable target in glioblastoma (GBM) therapy. Since AXL kinase inhibitors are about to get approval for clinical use, patients with a potential benefit from therapy targeting AXL need to be identified. We therefore assessed the expression pattern of Phospho-AXL (P-AXL), the biologically active form of AXL, in 90 patients with newly diagnosed GBM, which was found to be detectable in 67 patients (corresponding to 74%). We identified three main P-AXL expression patterns: i) exclusively in the tumor vasculature (13%), ii) in areas of hypercellularity (35%), or iii) both, in the tumor vasculature and in hypercellular areas of the tumor tissue (52%)...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637019/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#3
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637015/differential-metabonomic-profiles-of-primary-hepatocellular-carcinoma-tumors-from-alcoholic-liver-disease-hbv-infected-and-hcv-infected-cirrhotic-patients
#4
Ding Cao, Can Cai, Mingxin Ye, Junhua Gong, Menghao Wang, Jinzheng Li, Jianping Gong
Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC tumors from the three groups...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#5
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636293/-treatment-of-advanced-hepatocellular-carcinoma-novel-agents-and-role-of-local-therapy
#6
Louis Parisod, Rafael Duran, Alban Denys, Antonia Digklia
The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28636208/a-phase-i-trial-of-prn1008-a-novel-reversible-covalent-inhibitor-of-bruton-s-tyrosine-kinase-in-healthy-volunteers
#7
Patrick F Smith, Janakan Krishnarajah, Philip A Nunn, Ron J Hill, Dane Karr, D Tam, Mohammad Masjedizadeh, Jens O Funk, Steve G Gourlay
AIM: To evaluate the safety, tolerability, and PK/PD of PRN1008, a novel BTK inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50 to 1200 mg (n=6 active, 2 placebo per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 mg to 900 mg daily, either qd or bd for 10 days...
June 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28636094/characterization-of-clonal-philadelphia-negative-cytogenetic-abnormalities-in-a-large-cohort-of-chronic-myeloid-leukemia
#8
Xiangjun Chen, Jine Zheng, Kaiwei Liang, Yanli He, Wen Du, Juan Li, Wei Liu, Yanjie Hu, Junxia Yao
OBJECTIVES: Clonal Philadelphia-negative Cytogenetic Abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enrolled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31...
June 21, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28636039/a-convenient-method-for-multicolour-labelling-of-proteins-with-bodipy-fluorophores-via-tyrosine-residues
#9
Miffy H Y Cheng, Huguette Savoie, Francesca Bryden, Ross W Boyle
Fluorescence is an essential imaging modality for labelling and visualising cells and sub-cellular structures. Multicolour labelling is especially challenging due to differences in physicochemical and photophysical behaviour of structurally unrelated fluorophores in the heterogeneous environments found in sub-cellular compartments. Herein, we report the conjugation of three azide-bearing BODIPYs with similar core structures but widely different emission wavelengths (green, red and NIR) to tyrosine residues of a model globular protein (BSA) via a common linking methodology...
June 21, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#10
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#11
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28635227/-mechanism-and-clinical-efficacy-of-third-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-non-small-cell-lung-cancer
#12
X X Chen, C C Zhou
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, most of patients will develop resistance to TKIs treatment due to the emergence of the T790M mutation. The third-generation EGFR-TKI is highly selective and efficient for activating mutants (EGFR sensitive mutations) and resistance mutant (T790M+ ). This review summarizes the mechanism and clinical efficacy of the third-generation EGFR-TKI in NSCLC patients...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28635216/-ret-ptc-rearrangement-affects-multifocal-formation-of-papillary-thyroid-carcinoma
#13
X Zhang, X Su, W C Chen, Y Li, Z Y Yang, W Z Deng, T C Deng, A K Yang
Objective:RET/PTC gene rearrangement can lead to aberrant activation of tyrosine kinase receptors, which is a common mutation in papillary thyroid carcinoma (PTC). This study focuses on the association of RET/PTC rearrangements with PTC clinical factors. Methods: From January 2011 to December 2013, a total of 114 patients with PTC were enrolled in this study. Clinicopathological parameters, lifestyle, and thyroid hormone levels were collected. RET/PTC rearrangements were detected by TaqMan PCR and verified by Sanger sequencing...
June 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28634272/the-secreted-msp-domain-of-c-elegans-vapb-homolog-vpr-1-patterns-the-adult-striated-muscle-mitochondrial-reticulum-via-smn-1
#14
Jessica Schultz, Se-Jin Lee, Tim Cole, Hieu D Hoang, Jack Vibbert, Pauline A Cottee, Michael A Miller, Sung Min Han
The major sperm protein domain (MSPd) has an extracellular signaling function implicated in amyotrophic lateral sclerosis. Secreted MSPds derived from the C. elegans VAPB homolog VPR-1 promote mitochondrial localization to actin-rich I-bands in body wall muscle. Here we show that the nervous system and germ line are key MSPd secretion tissues. MSPd signals are transduced through the CLR-1 Lar-like tyrosine phosphatase receptor. We show that CLR-1 is expressed throughout the muscle plasma membrane, where it is accessible to MSPd within the pseudocoelomic fluid...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28634235/mechanistic-elucidation-of-the-mycofactocin-biosynthetic-radical-s-adenosylmethionine-protein-mftc
#15
Bulat Khaliullin, Richard Ayikpoe, Mason Tuttle, John A Latham
Ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways produce a diverse array of natural products. A subset of these pathways depend on radical S-adenosylmethionine (RS) proteins to modify the RiPP-produced peptide. Mycofactocin biosynthesis is one example of an RS protein-dependent RiPP pathway. Recently, it has been shown that MftC catalyzes the oxidative decarboxylation of the C-terminal tyrosine (Tyr30) on the mycofactocin precursor peptide MftA; however, this product has not been verified by techniques other than MS...
June 20, 2017: Journal of Biological Chemistry
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
#16
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/28634201/phosphoproteomic-profiling-reveals-alk-and-met-as-novel-actionable-targets-across-synovial-sarcoma-subtypes
#17
Emmy D G Fleuren, Myrella Vlenterie, Winette van der Graaf, Melissa H S Hillebrandt-Roeffen, James Blackburn, Xiuquan Ma, Howard Chan, Mandy C Magias, Anke van Erp, Laurens van Houdt, Sabri Cebeci, Amy van de Ven, Uta E Flucke, Erin E Heyer, David M Thomas, Christopher J Lord, Kieren D Marini, Vijesh Vaghjiani, Tim Mercer, Jason E Cain, Jianmin Wu, Yvonne M H Versleijen-Jonkers, Roger J Daly
Despite intensive multi-modal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases...
June 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28634183/syk-inhibitors-interfere-with-erythrocyte-membrane-modification-during-p-falciparum-growth-and-suppress-parasite-egress
#18
Antonella Pantaleo, Kristina R Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A Skorokhod, Huynh D Chien, Marta Ponzi, Lucia Bertuccini, Philip S Low, Francesco M Turrini
Band 3 (a.k.a. the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intra-erythrocytic stage of Plasmodium falciparum's life cycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#19
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/28633582/dopamine-and-light-effects-on-facial-emotion-recognition
#20
Elizabeth Cawley, Maria Tippler, Nicholas J Coupland, Chawki Benkelfat, Diane B Boivin, Marije Aan Het Rot, Marco Leyton
Bright light can affect mood states and social behaviours. Here, we tested potential interacting effects of light and dopamine on facial emotion recognition. Participants were 32 women with subsyndromal seasonal affective disorder tested in either a bright (3000 lux) or dim light (10 lux) environment. Each participant completed two test days, one following the ingestion of a phenylalanine/tyrosine-deficient mixture and one with a nutritionally balanced control mixture, both administered double blind in a randomised order...
June 1, 2017: Journal of Psychopharmacology
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