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https://www.readbyqxmd.com/read/28719896/update-on-the-diagnosis-and-prognosis-of-preeclampsia-with-the-aid-of-the-sflt-1-plgf-ratio-in-singleton-pregnancies
#1
Ignacio Herraiz, Elisa Llurba, Stefan Verlohren, Alberto Galindo
Preeclampsia (PE) is involved in a group of obstetrical conditions closely related by the presence of placental dysfunction (PD), which also includes intrauterine growth restriction and placental abruption. The timely and accurate recognition and management of PE are often challenging because diagnostic criteria are still based on nonspecific signs and symptoms and because common severity criteria correlate poorly with adverse maternal and fetal outcomes. The discovery of the role of angiogenesis-related factors - soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) - in the underlying pathophysiology of PD has marked an important step for improving its early diagnosis and prognosis assessment before gestational week 34...
July 19, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28719646/a-synergistic-negative-effect-of-gestational-smoke-exposure-and-small-litter-size-on-rat-placental-efficiency-vascularisation-and-angiogenic-factors-mrna-expression
#2
Zhen-Yan Chen, Ying Yao
Smoking increases the risk of pregnancy complications such as spontaneous abortion and low birth weight (LBW). By cigarette smoke exposure (gestational day, GD3-17), normal-litter-size pregnancy with low birth weight (NP-LBW) and small-litter-size pregnancy with normal birth weight (SP-NBW) in rats were induced. The placental weight in SP-NBW was twice the weight of the normal in contrast with the smaller placenta in NP-LBW. Compared with the normal, placental efficiency (expressed as fetus-to-placenta weight ratio) and placental vascularisation were significantly decreased in smoke exposed placentas with more obvious decrease in SP-NBW...
2017: PloS One
https://www.readbyqxmd.com/read/28719611/rna-sequencing-to-determine-the-contribution-of-kinase-receptor-transactivation-to-g-protein-coupled-receptor-signalling-in-vascular-smooth-muscle-cells
#3
Danielle Kamato, Venkata Vijayanand Bhaskarala, Nitin Mantri, Tae Gyu Oh, Dora Ling, Reearna Janke, Wenhua Zheng, Peter J Little, Narin Osman
G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR)...
2017: PloS One
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#4
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28719605/extracellular-phosphorylation-of-a-receptor-tyrosine-kinase-controls-synaptic-localization-of-nmda-receptors-and-regulates-pathological-pain
#5
Kenji Hanamura, Halley R Washburn, Sean I Sheffler-Collins, Nan L Xia, Nathan Henderson, Dipti V Tillu, Shayne Hassler, Daniel S Spellman, Guoan Zhang, Thomas A Neubert, Theodore J Price, Matthew B Dalva
Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28719467/pan-trk-immunohistochemistry-is-an-efficient-and-reliable-screen-for-the-detection-of-ntrk-fusions
#6
Jaclyn F Hechtman, Ryma Benayed, David M Hyman, Alexander Drilon, Ahmet Zehir, Denise Frosina, Maria E Arcila, Snjezana Dogan, David S Klimstra, Marc Ladanyi, Achim A Jungbluth
Activating neurotrophic tyrosine receptor kinase (NTRK) fusions, typically detected using nucleic-acid based assays, are highly targetable and define certain tumors. Here, we explore the utility of pan-TRK immunohistochemistry (IHC) to detect NTRK fusions. NTRK rearrangements were detected prospectively using MSK-IMPACT, a DNA-based next-generation sequencing assay. Transcription of novel NTRK rearrangements into potentially functional fusion transcripts was assessed via Archer Dx fusion assay. Pan-Trk IHC testing with mAb EPR17341 was performed on all NTRK rearranged cases and 20 cases negative for NTRK fusions on Archer...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28719349/identification-of-g2607a-mutation-in-egfr-gene-with-a-significative-rate-in-moroccan-patients-with-bladder-cancer
#7
W El Hamdani, K Hadami, M Bensaid, H El Ahanidi, A Ameur, A Filali Maltouf, M Abbar, M Attaleb, A Albouzidi, M El Mzibri
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718674/design-and-synthesis-of-a-novel-photoaffinity-probe-for-labelling-egf-receptor-tyrosine-kinases
#8
You-Guang Zheng, Xiao-Qing Wu, Jun Su, Ping Jiang, Liang Xu, Jian Gao, Bin Cai, Min Ji
The epidermal growth factor receptor (EGFR) and HER2 are two important tyrosine kinases that play crucial roles in signal transduction pathways that regulate numerous cellular functions including proliferation, differentiation, migration, and angiogenesis. In the past 20 years, many proteomic methods have emerged as powerful methods to evaluate proteins in biological processes and human disease states. Among them, activity-based protein profiling (ABPP) is one useful approach for the functional analysis of proteins...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28718672/synthesis-anticancer-and-apoptosis-inducing-activities-of-quinazoline-isatin-conjugates-epidermal-growth-factor-receptor-tyrosine-kinase-assay-and-molecular-docking-studies
#9
Adel S El-Azab, Abdullah Al-Dhfyan, Alaa A-M Abdel-Aziz, Laila A Abou-Zeid, Hamad M Alkahtani, Abdulrahman M Al-Obaid, Manal A Al-Gendy
A new series of quinazolinone compounds 16-34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC50: 10.38-38.67 μM and 9.91-15.77 μM, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cells lines were 70...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28718624/covalent-enzyme-inhibition-through-fluorosulfate-modification-of-a-non-catalytic-serine-residue
#10
Olugbeminiyi O Fadeyi, Lise R Hoth, Chulho Choi, Xidong Feng, Ariamala Gopalsamy, Erik C Hett, Robert E Kyne, Ralph P Robinson, Lyn H Jones
Irreversible enzyme inhibitors often utilize the reaction of a protein cysteine residue with an appropriately positioned electrophile (an acrylamide for example) in the ligand template. Cysteine residues are not always available for site-specific protein labeling and therefore new approaches are needed to expand the toolkit of appropriate electrophiles that target alternative amino acids. We have previously described the rational targeting of tyrosine residues in the active site of a protein (the mRNA decapping scavenger enzyme, DcpS) using inhibitors armed with sulfonyl fluoride electrophiles that additionally enabled the subsequent development of clickable probe technology to measure drug-target occupancy in live cells...
July 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28718377/downregulation-of-tyrosine-threonine-kinase-inhibits-tumor-growth-via-g2-m-arrest-in-human-endometrioid-endometrial-adenocarcinoma
#11
Jiamiao Zhang, Yan Jiang, Yu Zhao, Wanxue Wang, Yiran Xie, Huating Wang, Yihua Yang
Endometrial cancer is the most common gynecologic malignancy, about 80% of which is endometrial endometrioid carcinoma. Dysregulation of spindle assembly checkpoint plays a vital role in endometrial endometrioid carcinoma tumorigenesis and progression. The purpose of this study was to explore how tyrosine threonine kinase, a spindle assembly checkpoint-related protein, promotes the endometrial endometrioid carcinoma progression. We found that both messenger RNA and protein levels of tyrosine threonine kinase in endometrial endometrioid carcinoma tissues are higher than those in normal endometrial tissues, and its expression is associated with tumor stages...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28718011/case-series-on-the-association-between-blood-levels-and-side-effects-of-afatinib-maleate
#12
Junya Sato, Naoto Morikawa, Ryosuke Chiba, Satoru Nihei, Satoshi Moriguchi, Heisuke Saito, Kohei Yamauchi, Kenzo Kudo
PURPOSE: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug. METHODS: The study subjects were patients who were administered AFA for non-small cell lung cancer...
July 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28717712/egfr-mutations-in-latinos-from-the-united-states-and-latin-america
#13
Ariel Lopez-Chavez, Anish Thomas, Moses O Evbuomwan, Liqiang Xi, Guinevere Chun, Tatiana Vidaurre, Oscar Arrieta, George Oblitas, Ana Belen Oton, Alejandro R Calvo, Arun Rajan, Mark Raffeld, Seth M Steinberg, Lorena Arze-Aimaretti, Giuseppe Giaccone
PURPOSE: Epidermal growth factor receptor (EGFR) mutations confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). There are limited and conflicting reports on the frequency of EGFR mutations in Latinos. PATIENTS AND METHODS: Samples from 642 patients with NSCLC from seven institutions in the United States and Latin America were assessed for EGFR mutations (exons 18 to 21) at Clinical Laboratory Improvement Amendments-certified central laboratories...
October 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717642/lung-adenocarcinoma-patients-of-young-age-have-lower-egfr-mutation-rate-and-poorer-efficacy-of-egfr-tyrosine-kinase-inhibitors
#14
Shang-Gin Wu, Yih-Leong Chang, Chong-Jen Yu, Pan-Chyr Yang, Jin-Yuan Shih
Patients aged ≤50 years are rarely diagnosed with nonsmall cell lung cancer. We conducted a retrospective cohort study to understand the mutation status of EGFR and the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in young Asian patients with lung adenocarcinoma. We collected tumour specimens and malignant pleural effusions from lung adenocarcinoma patients from June 2005 to April 2014, recorded their clinical demographic data, and analysed EGFR mutations by reverse transcriptase PCR...
July 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28717217/tki-addicted-ros1-rearranged-cells-are-destined-to-survival-or-death-by-the-intensity-of-ros1-kinase-activity
#15
Hayato Ogura, Yuka Nagatake-Kobayashi, Jun Adachi, Takeshi Tomonaga, Naoya Fujita, Ryohei Katayama
ROS1 rearrangement is observed in 1-2% of non-small cell lung cancers (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers. However, emergence of acquired resistance to TKI is inevitable within a few years. Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells. Here we attempted to establish cabozantinib-resistant cells by N-ethyl-N-nitrosourea mutagenesis screening using CD74-ROS1-expressing Ba/F3 cells...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717206/an-amino-acid-signature-associated-with-obesity-predicts-2-year-risk-of-hypertriglyceridemia-in-school-age-children
#16
Sofia Moran-Ramos, Elvira Ocampo-Medina, Ruth Gutierrez-Aguilar, Luis Macías-Kauffer, Hugo Villamil-Ramírez, Blanca E López-Contreras, Paola León-Mimila, Joel Vega-Badillo, Roxana Gutierrez-Vidal, Ricardo Villarruel-Vazquez, Erandi Serrano-Carbajal, Blanca E Del-Río-Navarro, Adriana Huertas-Vázquez, Teresa Villarreal-Molina, Isabel Ibarra-Gonzalez, Marcela Vela-Amieva, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
Childhood obesity is associated with a number of metabolic abnormalities leading to increased cardiovascular risk. Metabolites can be useful as early biomarkers and new targets to promote early intervention beginning in school age. Thus, we aimed to identify metabolomic profiles associated with obesity and obesity-related metabolic traits. We used data from the Obesity Research Study for Mexican children (ORSMEC) in Mexico City and included a case control (n = 1120), cross-sectional (n = 554) and a longitudinal study (n = 301) of 6-12-year-old children...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717188/targeting-ptprz-inhibits-stem-cell-like-properties-and-tumorigenicity-in-glioblastoma-cells
#17
Akihiro Fujikawa, Hajime Sugawara, Taisaku Tanaka, Masahito Matsumoto, Kazuya Kuboyama, Ryoko Suzuki, Naomi Tanga, Atsuto Ogata, Makoto Masumura, Masaharu Noda
The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717073/interstitial-lung-disease-after-pleurodesis-for-malignant-pleural-effusion
#18
Norihito Yokoe, Eisuke Katsuda, Kenshi Kosaka, Rie Hamanaka, Ayako Matsubara, Masaki Nishimura, Hiroyuki Tanaka, Nobuhiro Asai, Ayumu Takahashi, Toshiki Kawamura, Tsuneo Ishiguchi, Etsuro Yamaguchi, Akihito Kubo
Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28717011/dysregulation-of-bcl-2-family-proteins-by-leukaemia-fusion-genes
#19
Lauren M Brown, Diane T Hanna, Seong L Khaw, Paul G Ekert
The genomic lesions that characterise acute lymphoblastic leukaemia in childhood include recurrent translocations that result in the expression of fusion proteins. These translocations typically involve the rearrangement of genes encoding tyrosine kinases, including receptor tyrosine kinase, cytokine receptors and transcription factors. These confer phenotypic changes that are the hallmarks of malignant transformation, including unrestricted proliferation and a relative resistance to apoptosis. In this review, we explore the molecular mechanisms that link these fusions to the control of cell death...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717004/two-tyrosine-residues-tyr-108-and-tyr-503-are-responsible-for-the-deprotonation-of-phenolic-substrates-in-vanillyl-alcohol-oxidase
#20
Tom A Ewing, Quoc-Thai Nguyen, Robert C Allan, Gudrun Gygli, Elvira Romero, Claudia Binda, Marco W Fraaije, Andrea Mattevi, Willem J H van Berkel
A number of oxidoreductases from the VAO/PCMH flavoprotein family catalyze the oxidation of para-substituted phenols. One of the best-studied is vanillyl alcohol oxidase (VAO) from the fungus Penicillium simplicissimum For oxidation of phenols by VAO to occur, they must first be bound in the enzyme's active site in their phenolate anion form. The crystal structure of VAO reveals that two tyrosine residues, Tyr-108 and Tyr-503, are positioned so as to facilitate this deprotonation. To investigate their role in catalysis, we created three VAO variants, Y108F, Y503F, and Y108F/Y503F, and studied their biochemical properties...
July 17, 2017: Journal of Biological Chemistry
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