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Tyrosine kinases

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https://www.readbyqxmd.com/read/27922739/tyrosine-kinase-aurora-kinase-and-leucine-aminopeptidase-as-attractive-drug-targets-in-anticancer-therapy-characterisation-of-their-inhibitors
#1
Joanna Ziemska, Jolanta Solecka
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies...
2016: Roczniki Państwowego Zakładu Higieny
https://www.readbyqxmd.com/read/27922693/a-novel-pdgf-receptor-inhibitor-eluting-stent-attenuates-in-stent-neointima-formation-in-a-rabbit-carotid-model
#2
Chen Huang, Haijun Mei, Min Zhou, Xiaobing Zheng
A novel drug-eluting stent (DES) is required to target vascular smooth muscle cells (SMCs) without harming endothelial cells (ECs). Platelet-derived growth factor (PDGF) is critical for the proliferation and migration of SMCs. Sunitinib [a PDGF receptor (PDGFR) tyrosine kinase inhibitor]‑eluting stents may therefore inhibit neointimal formation. The aim of the present study was to examine the stent‑based delivery of sunitinib in a rabbit carotid model; in addition, the effects of sunitinib were evaluated in vitro...
December 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922678/a-novel-rapid-point-of-care-test-for-lung-cancer-patients-to-detect-epidermal-growth-factor-receptor-gene-mutations-by-using-real-time-droplet-pcr-and-fresh-liquid-cytology-specimens
#3
Shiho Asaka, Akihiko Yoshizawa, Kazuyuki Matsuda, Akemi Yamaguchi, Hiroshi Yamamoto, Takayuki Shiina, Rie Nakata, Kaoru Ogawa, Meng Zhang, Takayuki Honda
Epidermal growth factor receptor gene (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). We developed a novel, rapid EGFR mutation assay using a real-time droplet-polymerase chain reaction machine (EGFR d-PCR assay). The purpose of this study was to validate the performance of the EGFR d-PCR assay using fresh liquid cytology specimens. We analyzed three major EGFR mutations (L858R in exon 21, E746_A750del in exon 19 and T790M in exon 20) in 80 fresh liquid cytology specimens of adenocarcinoma (ADC) or NSCLC-not otherwise specified (NOS) via the EGFR d-PCR assay and conventional real-time PCR assay using the therascreen® EGFR RGQ PCR kit (Therascreen assay)...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922668/dual-inhibition-using-cabozantinib-overcomes-hgf-met-signaling-mediated-resistance-to-pan-vegfr-inhibition-in-orthotopic-and-metastatic-neuroblastoma-tumors
#4
Estelle Daudigeos-Dubus, Ludivine Le Dret, Olivia Bawa, Paule Opolon, Albane Vievard, Irène Villa, Jacques Bosq, Gilles Vassal, Birgit Geoerger
MET is expressed on neuroblastoma cells and may trigger tumor growth, neoangiogenesis and metastasis. MET upregulation further represents an escape mechanism to various anticancer treatments including VEGF signaling inhibitors. We developed in vitro a resistance model to pan-VEGFR inhibition and explored the simultaneous inhibition of VEGFR and MET in neuroblastoma models in vitro and in vivo using cabozantinib, an inhibitor of the tyrosine kinases including VEGFR2, MET, AXL and RET. Resistance in IGR-N91-Luc neuroblastoma cells under continuous in vitro exposure pressure to VEGFR1-3 inhibition using axitinib was associated with HGF and p-ERK overexpression...
December 6, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27920724/insulin-induces-relaxation-and-decreases-hydrogen-peroxide-induced-vasoconstriction-in-human-placental-vascular-bed-in-a-mechanism-mediated-by-calcium-activated-potassium-channels-and-l-arginine-nitric-oxide-pathways
#5
Lissette Cabrera, Andrea Saavedra, Susana Rojas, Marcela Cid, Cristina Valenzuela, David Gallegos, Pamela Careaga, Emerita Basualto, Astrid Haensgen, Eduardo Peña, Coralia Rivas, Juan Carlos Vera, Victoria Gallardo, Leandro Zúñiga, Carlos Escudero, Luis Sobrevia, Mark Wareing, Marcelo González
HIGHLIGHTS Short-term incubation with insulin increases the L-arginine transport in HUVECs.Short-term incubation with insulin increases the NO synthesis in HUVECs.Insulin induces relaxation in human placental vascular bed.Insulin attenuates the constriction induced by hydrogen peroxide in human placenta.The relaxation induced by insulin is dependent on BKCa channels activity in human placenta. Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs)...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#6
REVIEW
Haijun Zhang
Lung cancer, ~80%-85% of which is non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Sensitizing mutations in epidermal growth factor receptor (EGFR) gene (EGFRm(+)), such as exon 19 deletions and exon 21 L858R point mutations, are the most important drivers in NSCLC patients. In this respect, small-molecule EGFR tyrosine kinase inhibitors (TKIs) have been designed and developed, which launched the era of targeted, personalized and precise medicine for lung cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27919989/teratogenic-effect-of-radotinib-case-report
#7
Juyoung Cheon, Jung Whan Ahn, Kyung Min Park, Guisera Lee, Yun Sung Jo
BACKGROUND: Simultaneous presentation of pregnancy and chronic myeloid leukemia (CML) is rare. Tyrosine kinase inhibitors (TKIs) are rarely used in pregnancy. There is almost no information on the effect of recently developed TKIs on the fetus. CASE REPORT: A 22-year-old woman became pregnant while using radotinib, a novel TKI for CML. She was concerned about the possible teratogenic effect of radotinib; hence the first pregnancy was terminated. The patient underwent full-term delivery at the second pregnancy...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919987/the-complete-loss-of-tyrosine-kinase-receptors-met-and-ron-is-a-poor-prognostic-factor-in-patients-with-extrahepatic-cholangiocarcinoma
#8
Yuki Hayashi, Junpei Yamaguchi, Toshio Kokuryo, Tomoki Ebata, Yukihiro Yokoyama, Tsuyoshi Igami, Gen Sugawara, Masato Nagino
BACKGROUND: Although the survival of patients with cholangiocarcinoma has improved, the prognosis remains unfavorable. The overexpression of mesenchymal-epithelial transition factor (MET) and recepteur d'origine nantais (RON) has been considered to be indicative of a poor prognosis in some types of cancer. On the other hand, some studies have shown that the expression of MET and RON is a favorable prognostic factor in certain types of tumors. MATERIALS AND METHODS: Based on the immunohistochemical analysis of MET and RON, 290 patients who underwent resection for extrahepatic cholangiocarcinoma were divided into three groups: MET/RON-negative, -intermediate, and -positive...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919943/kinomics-screening-identifies-aberrant-phosphorylation-of-cdc25c-in-flt3-itd-positive-aml
#9
Florian Perner, Tina M Schnöder, Thomas Fischer, Florian H Heidel
BACKGROUND/AIM: The presence of FLT3-Internal tandem duplications (ITDs) in human acute myeloid leukemia (AML) is associated with a dismal prognosis. Altered cell-cycle activity has been reported in FLT3-ITD-positive AML; however, the mechanisms by which this oncogene influences cell-cycle activity remained so far elusive. MATERIALS AND METHODS: A phospho-kinomic screen was used to identify downstream effectors of FLT3-ITD. Validation and functional characterization was performed by western blotting, cell-cycle analysis and apoptosis assays...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918717/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-chemotherapy-a-glimmer-of-hope
#10
Nele Van Der Steen, Christian Diego Rolfo, Patrick Pauwels, Godefridus J Peters, Elisa Giovannetti
No abstract text is available yet for this article.
December 5, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#11
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27918421/decreased-stat3-phosphorylation-mediates-cell-swelling-in-ammonia-treated-astrocyte-cultures
#12
Arumugam R Jayakumar, Kevin M Curtis, Kiran S Panickar, Nagarajarao Shamaladevi, Michael D Norenberg
Brain edema, due largely to astrocyte swelling, and the subsequent increase in intracranial pressure and brain herniation, are major complications of acute liver failure (ALF). Elevated level of brain ammonia has been strongly implicated in the development of astrocyte swelling associated with ALF. The means by which ammonia brings about astrocyte swelling, however, is incompletely understood. Recently, oxidative/nitrosative stress and associated signaling events, including activation of mitogen-activated protein kinases (MAPKs), as well as activation of the transcription factor, nuclear factor-kappaB (NF-κB), have been implicated in the mechanism of ammonia-induced astrocyte swelling...
December 2, 2016: Biology
https://www.readbyqxmd.com/read/27918253/placental-growth-factor-alone-or-in-combination-with-soluble-fms-like-tyrosine-kinase-1-as-an-aid-to-the-assessment-of-women-with-suspected-pre-eclampsia-systematic-review-and-economic-analysis
#13
Geoff K Frampton, Jeremy Jones, Micah Rose, Liz Payne
BACKGROUND: Pre-eclampsia (PE) prediction based on blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities can result in false-positive diagnoses. This may lead to unnecessary antenatal admissions and preterm delivery. Blood tests that measure placental growth factor (PlGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PlGF could aid prediction of PE if either were added to routine clinical assessment or used as a replacement for proteinuria testing...
November 2016: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/27918111/imatinib-accelerates-progenitor-cell-mediated-liver-regeneration-in-choline-deficient-ethionine-supplemented-diet-fed-mice
#14
András Rókusz, Edina Bugyik, Vanessza Szabó, Armanda Szücs, Sándor Paku, Péter Nagy, Katalin Dezső
Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline-deficient ethionine-supplemented diet (CDE)...
December 5, 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27917175/nuclear-localization-of-suppressor-of-cytokine-signaling-1-regulates-local-immunity-in-the-lung
#15
Jana Zimmer, Michael Weitnauer, Sébastien Boutin, Günter Küblbeck, Sabrina Thiele, Patrick Walker, Felix Lasitschka, Lars Lunding, Zane Orinska, Christina Vock, Bernd Arnold, Michael Wegmann, Alexander Dalpke
Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet, the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGL(tg) mice). Whereas mice fully deficient for SOCS1 die within the first 3 weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1(-/-)MGL(tg) mice) were rescued from early lethality...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916840/ligand-activation-of-tam-family-receptors-implications-for-tumor-biology-and-therapeutic-response
#16
REVIEW
Viralkumar Davra, Stanley G Kimani, David Calianese, Raymond B Birge
The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology...
November 29, 2016: Cancers
https://www.readbyqxmd.com/read/27916828/enhancing-anticancer-effect-of-gefitinib-across-the-blood-brain-barrier-model-using-liposomes-modified-with-one-%C3%AE-helical-cell-penetrating-peptide-or-glutathione-and-tween-80
#17
Kuan-Hung Lin, Shu-Ting Hong, Hsiang-Tsui Wang, Yu-Li Lo, Anya Maan-Yuh Lin, James Chih-Hsin Yang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916795/first-and-second-line-targeted-systemic-therapy-in-hepatocellular-carcinoma-an-update-on-patient-selection-and-response-evaluation
#18
REVIEW
Johann von Felden, Kornelius Schulze, Ines Gil-Ibanez, Tobias Werner, Henning Wege
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy...
November 28, 2016: Diagnostics
https://www.readbyqxmd.com/read/27915976/strategies-to-strike-survival-networks-in-cancer
#19
Marzia Pennati, Graziella Cimino-Reale, Laura Gatti, Giuliana Cassinelli
The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27915477/treadmill-exercise-improves-memory-function-depending-on-circadian-rhythm-changes-in-mice
#20
Dong Sup Hwang, Hyo Bum Kwak, Il Gyu Ko, Sung Eun Kim, Jun Jang Jin, Eun Sang Ji, Hyun Hee Choi, Oh Young Kwon
PURPOSE: Exercise enhances memory function by increasing neurogenesis in the hippocampus, and circadian rhythms modulate synaptic plasticity in the hippocampus. The circadian rhythm-dependent effects of treadmill exercise on memory function in relation with neurogenesis were investigated using mice. METHODS: The step-down avoidance test was used to evaluate short-term memory, the 8-arm maze test was used to test spatial learning ability, and 5-bromo-2'-deoxyuridine immunofluorescence was used to assess neurogenesis...
November 2016: International Neurourology Journal
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