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https://www.readbyqxmd.com/read/28817624/ephb4-ephrinb2-therapeutics-in-rhabdomyosarcoma
#1
Matthew E Randolph, Megan M Cleary, Zia Bajwa, Matthew N Svalina, Michael C Young, Atiya Mansoor, Pali Kaur, Carol J Bult, Martin W Goros, Joel E Michalek, Sunny Xiang, James Keck, Valery Krasnoperov, Parkash Gill, Charles Keller
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma affecting children and is often diagnosed with concurrent metastases. Unfortunately, few effective therapies have been discovered that improve the long-term survival rate for children with metastatic disease. Here we determined effectiveness of targeting the receptor tyrosine kinase, EphB4, in both alveolar and embryonal RMS either directly through the inhibitory antibody, VasG3, or indirectly by blocking both forward and reverse signaling of EphB4 binding to EphrinB2, cognate ligand of EphB4...
2017: PloS One
https://www.readbyqxmd.com/read/28817576/gestational-diabetes-mellitus-is-associated-with-increased-pro-migratory-activation-of-vascular-endothelial-growth-factor-receptor-2-and-reduced-expression-of-vascular-endothelial-growth-factor-receptor-1
#2
Felipe Troncoso, Jesenia Acurio, Kurt Herlitz, Claudio Aguayo, Patricio Bertoglia, Enrique Guzman-Gutierrez, Marco Loyola, Marcelo Gonzalez, Meriem Rezgaoui, Gernot Desoye, Carlos Escudero
Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18)...
2017: PloS One
https://www.readbyqxmd.com/read/28817487/inhibiting-protein-tyrosine-phosphatase-1b-to-improve-regenerative-functions-of-endothelial-cells
#3
Yuan Wang, Feng Yan, Wenjing Zhang, Shu Pang, Fan Jiang
Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor- and vascular endothelial growth factor receptor-dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration, and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817438/alternatively-activated-macrophages-drive-browning-of-white-adipose-tissue-in-burns
#4
Abdikarim Abdullahi, Christopher Auger, Mile Stanojcic, David Patsouris, Alexandra Parousis, Slava Epelman, Marc G Jeschke
OBJECTIVE: The aim of this study was to uncover the mediators and mechanistic events that facilitate the browning of white adipose tissue (WAT) in response to burns. BACKGROUND: In hypermetabolic patients (eg, burns, cancer), the browning of WAT has presented substantial clinical challenges related to cachexia, atherosclerosis, and poor clinical outcomes. Browning of the adipose tissue has recently been found to induce and sustain hypermetabolism. Although browning appears central in trauma-, burn-, or cancer-induced hypermetabolic catabolism, the mediators are essentially unknown...
August 16, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#5
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817370/conko-005-adjuvant-chemotherapy-with-gemcitabine-plus-erlotinib-versus-gemcitabine-alone-in-patients-after-r0-resection-of-pancreatic-cancer-a-multicenter-randomized-phase-iii-trial
#6
Marianne Sinn, Marcus Bahra, Torsten Liersch, Klaus Gellert, Helmut Messmann, Wolf Bechstein, Dirk Waldschmidt, Lutz Jacobasch, Martin Wilhelm, Bettina M Rau, Robert Grützmann, Arndt Weinmann, Georg Maschmeyer, Uwe Pelzer, Jens M Stieler, Jana K Striefler, Michael Ghadimi, Sven Bischoff, Bernd Dörken, Helmut Oettle, Hanno Riess
Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28816950/pemetrexed-carboplatin-with-intercalated-icotinib-in-the-treatment-of-patient-with-advanced-egfr-wild-type-lung-adenocarcinoma-a-case-report
#7
Tongpeng Xu, Hao Wu, Shidai Jin, Huang Min, Zhihong Zhang, Yongqian Shu, Wei Wen, Renhua Guo
RATIONALE: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. PATIENT CONCERNS: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. DIAGNOSES: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816796/intrathecal-infusion-of-haploidentical-nondonor-lymphocytes-for-central-nervous-system-leukemic-relapse-after-haploidentical-hematopoietic-stem-cell-transplantation
#8
Azusa Mayumi, Akihisa Sawada, Aya Ioi, Kohei Higuchi, Mariko Shimizu, Maho Sato, Masahiro Yasui, Masami Inoue
Leukemic relapse in the central nervous system (CNS) after conventional treatment is associated with a poor prognosis. The effectiveness and safety of IV infusion of human leukocyte antigen (HLA)-mismatched lymphocytes for leukemia, and intrathecal (IT) infusion of HLA-mismatched lymphocytes for cerebrospinal fluid (CSF) dissemination of medulloblastoma have been reported. A 13-year-old girl (HLA-A31) was diagnosed as relapsing from Philadelphia chromosome-positive acute leukemia in the CNS after receiving chemotherapy, tyrosine kinase inhibitors, haploidentical hematopoietic stem cell transplantation (HSCT) from her father (HLA-A31), and craniospinal irradiation...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28816549/implications-of-bcl-2-and-its-interplay-with-other-molecules-and-signaling-pathways-in-prostate-cancer-progression
#9
Ju-Ha Kim, Hyemin Lee, Eun Ah Shin, Dong Hee Kim, Jhin Baek Choi, Sung-Hoon Kim
Among several genetic alterations involved in the progression of prostate cancer, B cell lymphoma gene number 2 (BCL-2) is an important target molecule in the progression of androgen-independent prostate cancer (AIPC) after androgen ablation or castration. Nevertheless, the molecular mechanism of BCL-2 in prostate cancer progression remains elusive and controversial. In the current review, we discuss the critical role of BCL-2 in the carcinogenesis of prostate cancer with experimental evidences on the BCL-2 molecular networks in AIPC and androgen-dependent prostate cancer (ADPC) and subsequently suggest perspective research targeting BCL-2...
August 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28816243/dopamine-synthesis-capacity-is-associated-with-d2-3-receptor-binding-but-not-dopamine-release
#10
Anne S Berry, Vyoma D Shah, Daniella J Furman, Robert L White, Suzanne L Baker, James P O'Neil, Mustafa Janabi, Mark D'Esposito, William J Jagust
Positron Emission Tomography (PET) imaging allows the estimation of multiple aspects of dopamine function including dopamine synthesis capacity, dopamine release, and D2/3 receptor binding. Though dopaminergic dysregulation characterizes a number of neuropsychiatric disorders including schizophrenia and addiction, there has been relatively little investigation into the nature of relationships across dopamine markers within healthy individuals. Here we used PET imaging in 40 healthy adults to compare, within individuals, estimates of dopamine synthesis capacity (Ki) using 6-[(18)F]fluoro-l-m-tyrosine ([(18)F]FMT; a substrate for aromatic amino acid decarboxylase), baseline D2/3 receptor binding potential using [(11)C]raclopride (a weak competitive D2/3 receptor antagonist), and dopamine release using [(11)C]raclopride paired with oral methylphenidate administration...
August 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28815968/discovery-of-naphthyl-n-acylhydrazone-p38%C3%AE-mapk-inhibitors-with-in-vivo-anti-inflammatory-and-anti-tnf-%C3%AE-activity
#11
Rosana H C N Freitas, Natália M Cordeiro, Patrícia R Carvalho, Marina A Alves, Isabella A Guedes, Tayna S Valerio, Laurent E Dardenne, Lídia M Lima, Eliezer J Barreiro, Patrícia D Fernandes, Carlos A M Fraga
Protein kinases constitute attractive therapeutic targets for development of new prototypes to treat different chronic diseases. Several available drugs, like tinibs, are tyrosine kinase inhibitors, meanwhile, inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase (MAPK) are still trying to overcome some problems in one of the steps of clinical development to become drugs. So, here we reported the synthesis, the in vitro kinase inhibitory profile, docking studies and the evaluation of anti-inflammatory profile of new naphthyl-N-acylhydrazone derivatives using animal models...
August 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28815757/first-line-treatment-selection-and-early-monitoring-patterns-in-chronic-phase-chronic-myeloid-leukemia-in-routine-clinical-practice-simplicity
#12
Stuart L Goldberg, Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010-September 02 2015) are reported...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815728/effects-of-bifenthrin-exposure-on-the-estrogenic-and-dopaminergic-pathways-in-zebrafish-embryos-and-juveniles
#13
Luísa Becker Bertotto, Jaben Richards, Jay Gan, David Christopher Volz, Daniel Schlenk
Bifenthrin (BF) is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of BF increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic (DA) pathway components. DA neurons can indirectly regulate E2 biosynthesis, suggesting that BF may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Since embryos do not have a complete HPG axis, the hypothesis that BF impairs DA regulation was tested in embryonic and one-month old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0...
August 16, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#14
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28815507/using-purified-tyrosine-site-specific-recombinases-in-vitro-to-rapidly-construct-and-diversify-metabolic-pathways
#15
Wei Liu, Laura R Tuck, Jon Marles Wright, Yizhi Cai
The site-specific recombinase Cre was previously reported to have in vitro activity. Here, we describe the method of purifying two new tyrosine site-specific recombinases VCre and Dre along with Cre by nickel affinity chromatography. We proved the in vitro function of the VCre and Dre on their respective conditional recombination sites. We also developed a methodology to one-step construct and optimize the productivity of a biosynthetic pathway through the combinatorial integration of promoters into a plasmid-encoded pathway by simply incubating a DNA mixture with recombinase system at 37 °C in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815493/dual-recombinase-mediated-cassette-exchange-by-tyrosine-site-specific-recombinases
#16
Eugenia Voziyanova, Rachelle P Anderson, Yuri Voziyanov
Recombinase-mediated cassette exchange, or RMCE, is a genome engineering tool that can be used to swap DNA fragments of interest between two DNA molecules. In a variation of RMCE, called dual RMCE, the exchange of DNA fragments is mediated by two recombinases in contrast to one recombinase in the classic RMCE reaction. Under optimal conditions, the efficiency of dual RMCE can be quite high: up to ~45% of the transfected cells depending on the recombinase pair used to mediate the replacement reaction. Here we describe protocols for preparing for, performing, and optimizing the parameters of dual RMCE...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815478/o-2-18-f-fluoroethyl-l-tyrosine-pet-in-gliomas-influence-of-data-processing-in-different-centres
#17
Christian P Filss, Nathalie L Albert, Guido Böning, Elena Rota Kops, Bogdana Suchorska, Gabriele Stoffels, Norbert Galldiks, Nadim J Shah, Felix M Mottaghy, Peter Bartenstein, Jörg C Tonn, Karl-Josef Langen
BACKGROUND: PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) is an established method for brain tumour diagnostics, but data processing varies in different centres. This study analyses the influence of methodological differences between two centres for tumour characterization with (18)F-FET PET using the same PET scanner. Methodological differences between centres A and B in the evaluation of (18)F-FET PET data were identified for (1) framing of PET dynamic data, (2) data reconstruction, (3) cut-off values for tumour delineation to determine tumour-to-brain ratios (TBR) and tumour volume (Tvol) and (4) ROI definition to determine time activity curves (TACs) in the tumour...
August 16, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#18
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28814805/intercalating-and-maintenance-gefitinib-plus-chemotherapy-versus-chemotherapy-alone-in-selected-advanced-non-small-cell-lung-cancer-with-unknown-egfr-status
#19
Hong Jian, Wei Li, Zhiyong Ma, Jianjin Huang, Jifeng Feng, Yong Song, Beili Gao, Huili Zhu, Min Tao, Chong Bai, Shenglin Ma, Hongming Pan, Shukui Qin, Dong Hua, Yongfeng Yu, Shun Lu
Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m(2)) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15-25 of each cycle until disease progress (n = 109)...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814789/differential-oxidation-of-protein-tyrosine-phosphatases-during-zebrafish-caudal-fin-regeneration
#20
Wei Wu, Alexander James Hale, Simone Lemeer, Jeroen den Hertog
Zebrafish have the capacity to regenerate lost tissues and organs. Amputation of the caudal fin results in a rapid, transient increase in H2O2 levels emanating from the wound margin, which is essential for regeneration, because quenching of reactive oxygen species blocks regeneration. Protein-tyrosine phosphatases (PTPs) have a central role in cell signalling and are susceptible to oxidation, which results in transient inactivation of their catalytic activity. We hypothesized that PTPs may become oxidized in response to amputation of the caudal fin...
August 16, 2017: Scientific Reports
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