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https://www.readbyqxmd.com/read/29793113/assessment-of-the-risk-of-antiangiogenic-agents-before-and-after-surgery
#1
REVIEW
Christina E Bailey, Alexander A Parikh
Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types, and thus, antiangiogenic agents have been studied for many years as potential therapeutic agents. Many different antiangiogenic agents, including monoclonal antibodies and multi-targeted tyrosine kinase inhibitors (TKIs), have been approved for various oncology indications, and promising clinical activity has been demonstrated. However, some of these agents have also been associated with serious safety concerns...
May 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29793020/epha2-stimulates-vcam-1-expression-through-calcium-dependent-nfat1-activity
#2
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29792933/role-of-neuronal-nitric-oxide-synthase-in-slowly-progressive-dopaminergic-neurodegeneration-in-the-zitter-rat
#3
Ayuka Ehara, Kazuhiko Nakadate, Hiroyuki Sugimoto, Kanji Yoshimoto, Shuichi Ueda
Neuronal nitric oxide synthase (nNOS) is involved in nigrostriatal dopaminergic (DA) neurodegeneration. However, little is known about the distribution patterns and functions of nNOS in slowly progressive DA neurodegeneration. Here we describe the spatiotemporal change in nNOS expression over the course of neurodegeneration and the effect of short- or long-term treatment with the nNOS inhibitor, 7-nitroindazole (7-NI), in zitter (zi/zi) rats. In the substantia nigra pars compacta (SNc), nNOS expression was significantly increased with progression of neurodegeneration...
May 21, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29792848/subthalamic-nucleus-deep-brain-stimulation-protects-neurons-by-activating-autophagy-via-pp2a-inactivation-in-a-rat-model-of-parkinson-s-disease
#4
Ting-Ting Du, Ying-Chuan Chen, Yong-Quan Lu, Fan-Gang Meng, Hui Yang, Jian-Guo Zhang
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum...
May 21, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29792806/fate-of-fluorescence-labels-their-adsorption-and-desorption-kinetics-to-silver-nanoparticles
#5
Claudia Kästner, Linda Böhmert, Albert Braeuning, Alfonso Lampen, Andreas F Thünemann
Silver nanoparticles are among the most widely used und produced nanoparticles. Due to their frequent application in consumer products, the assessment of their toxicological potential has seen a renewed importance. A major difficulty is the traceability of nanoparticles in in vitro and in vivo experiments. Even if the particles are labeled, for example by a fluorescent marker, the dynamic exchange of ligands often prohibits their spatial localization. Our study provides an insight into the adsorption and desorption kinetics of two different fluorescent labels on silver nanoparticles with a core radius of 3 nm by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and fluorescence spectroscopy...
May 24, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29792724/a-systematic-understanding-of-signaling-by-erbb2-in-cancer-using-phosphoproteomics
#6
C Sidhanth, P Manasa, S Krishnapriya, S Sneha, S Bindhya, R P Nagare, M Garg, T S Ganesan
ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%-30%) and gastric cancer (10%-20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins...
May 24, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29792702/peniisocoumarins-a-j-isocoumarins-from-penicillium-commune-qqf-3-an-endophytic-fungus-of-the-mangrove-plant-kandelia-candel
#7
Runlin Cai, Yingnan Wu, Senhua Chen, Hui Cui, Zhaoming Liu, Chunyuan Li, Zhigang She
Ten new isocoumarins, named peniisocoumarins A-J (1-9 and 11), along with three known analogues (10, 12, and 13) were obtained from the fermentation of an endophytic fungus, Penicillium commune QQF-3, which was isolated from a fresh fruit of the mangrove plant Kandelia candel. Their structures were elucidated through extensive spectroscopic analysis. The absolute configurations of 1-7 were determined by single-crystal X-ray diffraction and modified Mosher's method, and those of 8, 9, and 11 were assigned on the basis of experimental and calculated electronic circular dichroism data...
May 24, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29792672/biosynthesis-of-lincosamide-antibiotics-reactions-associated-with-degradation-and-detoxification-pathways-play-a-constructive-role
#8
Daozhong Zhang, Zhijun Tang, Wen Liu
Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function...
May 24, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29792386/disparate-effects-of-shb-gene-deficiency-on-disease-characteristics-in-murine-models-of-myeloid-b-cell-and-t-cell-leukemia
#9
Maria Jamalpour, Xiujuan Li, Karin Gustafsson, Jeffrey W Tyner, Michael Welsh
The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#10
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792121/abcg2-polymorphism-rs2231142-and-hypothyroidism-in-metastatic-renal-cell-carcinoma-patients-treated-with-sunitinib
#11
Emilie Werbrouck, Julie Bastin, Diether Lambrechts, Annelies Verbiest, Thomas Van Brussel, Evelyne Lerut, Jean-Pascal Machiels, Vincent Verschaeve, Vincent Richard, Philip R Debruyne, Brigitte Decallonne, Patrick Schöffski, Oliver Bechter, Pascal Wolter, Benoit Beuselinck
Background and aim Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics. Patients and methods We included 79 mRCC patients who started sunitinib between November 2005 and March 2016...
May 23, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29791483/structural-study-reveals-the-temperature-dependent-conformational-flexibility-of-tk-ptp-a-protein-tyrosine-phosphatase-from-thermococcus-kodakaraensis-kod1
#12
Hye-Yeoung Yun, Jinhyuk Lee, Hyunmin Kim, Hyojung Ryu, Ho-Chul Shin, Byung-Ha Oh, Bonsu Ku, Seung Jun Kim
Protein tyrosine phosphatases (PTPs) originating from eukaryotes or bacteria have been under intensive structural and biochemical investigation, whereas archaeal PTP proteins have not been investigated extensively; therefore, they are poorly understood. Here, we present the crystal structures of Tk-PTP derived from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1, in both the active and inactive forms. Tk-PTP adopts a common dual-specificity phosphatase (DUSP) fold, but it undergoes an atypical temperature-dependent conformational change in its P-loop and α4-α5 loop regions, switching between the inactive and active forms...
2018: PloS One
https://www.readbyqxmd.com/read/29791298/the-influence-of-dopamine-on-cognitive-flexibility-is-mediated-by-functional-connectivity-in-young-but-not-older-adults
#13
Anne S Berry, Vyoma D Shah, William J Jagust
Dopaminergic signaling in striatum is strongly implicated in executive functions including cognitive flexibility. However, there is a paucity of multimodal research in humans defining the nature of relationships between endogenous dopamine, striatal network activity, and cognition. Here, we measured dopamine synthesis capacity in young and older adults using the PET tracer 6-[18 F]fluoro-l- m-tyrosine and examined its relationship with cognitive performance and functional connectivity during an fMRI study of task switching...
May 23, 2018: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/29791083/structure-and-biocatalytic-scope-of-coclaurine-n-methyltransferase
#14
Matthew Bennett, Mark Thompson, Sarah Shepherd, Mark Dunstan, Abigail Herbert, Duncan Smith, Victoria Cronin, Binuraj Menon, Colin Levy, Jason Micklefield
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites which have been exploited to develop analgesics, antibiotics, antitumor agents and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture...
May 23, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29790946/a-microbial-endocrinology-based-simulated-small-intestinal-medium-for-the-evaluation-of-neurochemical-production-by-gut-microbiota
#15
Daniel N Villageliú, Sharon Rasmussen, Mark Lyte
Microbial endocrinology represents the union of microbiology and neurobiology and is concerned with the ability of neurochemicals to serve as an evolutionary-based language between host and microbiota in health and disease. The recognition that microorganisms produce, modify and respond to the same neurochemicals utilized in the various signaling pathways of their mammalian hosts is increasingly being recognized as a mechanism by which the host and microbiota may interact to influence the progression of infectious disease as well as influence behavior through the microbiota-gut-brain axis...
May 21, 2018: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/29790812/-express-nav1-7-is-phosphorylated-by-fyn-tyrosine-kinase-which-modulates-channel-expression-and-gating-in-a-cell-type-dependent-manner
#16
Yangyang Li, Tengteng Zhu, Huan Yang, Sulayman Dib-Hajj, Stephen Waxman, Ye Yu, Tian-Le Xu, Xiaoyang Cheng
Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, a Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29790264/immune-responses-against-tumor-associated-antigen-derived-cytotoxic-t-lymphocyte-epitopes-in-cholangiocarcinoma-patients
#17
Akihiko Kida, Eishiro Mizukoshi, Toshikatsu Tamai, Takeshi Terashima, Masaaki Kitahara, Kuniaki Arai, Tatsuya Yamashita, Kazumi Fushimi, Masao Honda, Shuichi Kaneko
BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumor-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR)...
May 23, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29790168/periodontitis-and-placental-growth-factor-in-oral-fluids-are-early-pregnancy-predictors-of-gestational-diabetes-mellitus
#18
Alejandra Chaparro, Edgardo Zúñiga, Manuel Varas-Godoy, Daniela Albers, Valeria Ramírez, Marcela Hernández, Juan P Kusanovic, Stephanie Acuña-Gallardo, Gregory Rice, Sebastián E Illanes
BACKGROUND: Gestational Diabetes Mellitus (GDM) affects around 7-10% of all pregnancies. Early detection of predisposition to GDM is the first step in developing efficacious preventive treatment. The objective of the present study was to establish the utility of placental proteins presents in oral fluids (gingival crevicular fluid [GCF] and saliva), and periodontal disease status as early pregnancy predictors of GDM. MATERIAL AND METHODS: A nested case control within a prospective cohort was conducted...
May 22, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29790151/irreversible-modifications-of-receptor-tyrosine-kinases
#19
Matthew Kreitman, Ashish Noronha, Yosef Yarden
Each group of the 56 receptor tyrosine kinases (RTK) binds with one or more soluble growth factors and coordinates a vast array of cellular functions. These outcomes are tightly regulated by inducible post-translational events, such as tyrosine phosphorylation, ubiquitination, ectodomain shedding and regulated intramembrane proteolysis. Because of the delicate balance required for appropriate RTK function, cells may become pathogenic upon dysregulation of RTKs themselves or their post-translational covalent modifications...
May 22, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29789968/exploring-the-mechanistic-insights-of-cas-scaffolding-protein-family-member-4-with-protein-tyrosine-kinase-2-in-alzheimer-s-disease-by-evaluating-protein-interactions-through-molecular-docking-and-dynamic-simulations
#20
Mubashir Hassan, Saba Shahzadi, Hany Alashwal, Nazar Zaki, Sung-Yum Seo, Ahmed A Moustafa
Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites...
May 22, 2018: Neurological Sciences
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