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Michaël Duruisseaux, Anne McLeer-Florin, Martine Antoine, Sanaz Alavizadeh, Virginie Poulot, Roger Lacave, Nathalie Rabbe, Jacques Cadranel, Marie Wislez
Invasive mucinous lung adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with no effective treatment option in advanced disease. KRAS mutations occur in 28-87% of the cases. NRG1 fusions were recently discovered in KRAS-negative IMA cases and otherwise negative for known driver oncogenes and could represent an attractive therapeutic target. Published data suggest that NRG1 fusions occur essentially in nonsmoking Asian women. From an IMA cohort of 25 French patients of known ethnicity, driver oncogenes EGFR, KRAS, BRAF, ERBB2 mutations, and ALK and ROS1 rearrangements presence were analyzed...
October 21, 2016: Cancer Medicine
Shuhang Wang, Yongping Song, Feifei Yan, Delong Liu
The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy...
October 21, 2016: Frontiers of Medicine
Andriy Bilichak, Andrey Golubov, Igor Kovalchuk
The discovery of small RNAs in plants and animals almost two decades ago attracted a significant interest towards epigenetic regulation of gene expression and the practical implementation of the gained knowledge in applied studies. New and sometimes unexpected functions have been ascribed to sRNAs almost every couple of years since their discovery, hence indicating that the complete role of sRNAs in plant and animal physiology is still barely understood. Next-generation sequencing technologies allow to generate high-resolution profiles of sRNAs for the consequent analysis and possibly to discover novel functions of sRNAs...
2017: Methods in Molecular Biology
K L Yew, Z Kang, A Anum
Coronary artery anomalies are often discovered incidentally during cardiac catheterization or computed tomography coronary angiography and may involve the affected coronary artery origin and its course. Coronary artery anomalies are associated with congenital heart disease. The affected coronary arteries may have an unusual high take off origin, origin from contralateral or non-coronary sinus, origin from the pulmonary artery, single coronary system or coronary artery fistula.
August 2016: Medical Journal of Malaysia
Roman Shrestha, Pramila Karki, Tania B Huedo-Medina, Michael Copenhaver
Neurocognitive impairment (NCI) and treatment engagement (TE) have been shown to significantly predict antiretroviral therapy (ART) adherence, but no studies have explored the ways and the extent to which similar outcomes might occur when these factors operate together, particularly for people who use drugs (PWUDs). We sought to discover whether TE moderated the effect of NCI on adherence to ART in HIV-infected individuals. One hundred sixteen HIV-infected, methadone-maintained people who reported HIV risk behaviors were enrolled in the study...
September 22, 2016: Journal of the Association of Nurses in AIDS Care: JANAC
Shan Qian, Tao He, Wei Wang, Yanying He, Man Zhang, Lingling Yang, Guobo Li, Zhouyu Wang
Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated kynurenine pathway of tryptophan degradation is identified as an important immune effector pathway in the tumor cells to escape a potentially effective immune response. IDO1 is an attractive target for anticancer therapy and the discovery of IDO1 inhibitors has been intensely ongoing in both academic research laboratories and pharmaceutical organizations. Our study discovered that 1H-indazole was a novel key pharmacophore with potent IDO1 inhibitory activity. A series of new 1H-indazole derivatives were synthesized and determined the enzyme inhibitory activities, and the compound 2g exhibited the highest activity with an IC50 value of 5...
October 6, 2016: Bioorganic & Medicinal Chemistry
F Heran Dreyfus, O Galatoire, P Koskas, F Lafitte, E Nau, O Bergès
Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding)...
October 18, 2016: Journal Français D'ophtalmologie
Xi Chen, Heng Qiu, Chao Wang, Yu Yuan, Jennifer Tickner, Jiake Xu, Jun Zou
Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction...
October 8, 2016: Cytokine & Growth Factor Reviews
Gloria Isani, Enea Ferlizza, Aurora Cuoghi, Elisa Bellei, Emanuela Monari, Barbara Bianchin Butina, Carolina Castagnetti
Characterisation of the physiologic equine amniotic fluid (AF) proteome is a prerequisite to study its changes during diseases and discover new biomarkers. The aim of this study was to identify by a proteomic approach the most abundant proteins of equine AF. AF samples were collected at parturition from 24 healthy mares that delivered healthy foals. All samples were subjected to sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) on 4-12% gels. A pool of the 24 samples, after SDS-PAGE, was cut in 25 slices, trypsin-digested and analysed by mass spectrometry (MS) for protein identification...
October 11, 2016: Animal Reproduction Science
Zhigang Sui, Yejing Weng, Qun Zhao, Nan Deng, Fei Fang, Xudong Zhu, Yichu Shan, Lihua Zhang, Yukui Zhang
The cartilage zone of the velvet antler is richly vascularized, this being a major difference to the classical cartilage, in which there are no blood vessels. Angiogenesis and rapid growth of vasculature in velvet antler cartilage (VAC) make it an ideal model for discovering the novel angiogenic regulatory factors. However, the proteomic analysis of VAC is challenging due to the serious interference of proteoglycans (PGs) and collagens. To achieve a comprehensive proteome characterization of VAC, herein, we developed an ionic liquid-based method using 1-dodecyl-3-methylimidazolium chloride ([C12-mim]Cl) for selective extraction of cellular proteins from VAC...
December 1, 2016: Talanta
María Asunción López-Bascón, Mónica Calderón-Santiago, Feliciano Priego-Capote
A novel class of endogenous mammalian lipids endowed with antidiabetic and anti-inflammatory properties has been recently discovered. These are fatty acid esters of hydroxy fatty acids (FAHFAs) formed by condensation between a hydroxy fatty acid and a fatty acid. FAHFAs are present in human serum and tissues at low nanomolar concentrations. Therefore, high sensitivity and selectivity profiling analysis of these compounds in clinical samples is demanded. An automated qualitative and quantitative method based on on-line coupling between solid phase extraction and liquid chromatography-tandem mass spectrometry has been here developed for determination of FAHFAs in serum with the required sensitivity and selectivity...
November 2, 2016: Analytica Chimica Acta
Pierre Dehoux, Jean Christophe Marvaud, Amr Abouelleil, Ashlee M Earl, Thierry Lambert, Catherine Dauga
BACKGROUND: Clostridium bolteae and Clostridium clostridioforme, previously included in the complex C. clostridioforme in the group Clostridium XIVa, remain difficult to distinguish by phenotypic methods. These bacteria, prevailing in the human intestinal microbiota, are opportunistic pathogens with various drug susceptibility patterns. In order to better characterize the two species and to obtain information on their antibiotic resistance genes, we analyzed the genomes of six strains of C...
October 21, 2016: BMC Genomics
Carly B Garrison, Kristin J Lastwika, Yuzheng Zhang, Christopher I Li, Paul D Lampe
Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding of signaling response during stress and disease. Large datasets, such as those obtained in high-dimensional proteomic studies, can be leveraged for pathway analysis to discover or describe the biological implications of clinical disease states. Obesity is a worldwide epidemic that is considered a risk factor for numerous other diseases. We performed analysis on plasma proteomic data from 3 separate sample sets of post-menopausal women to identify the pathways that are altered in subjects with a high body mass index (BMI) compared to normal BMI...
October 21, 2016: Journal of Proteome Research
Thomas J Lawton, Amy C Rosenzweig
Nature utilizes two groups of enzymes to catalyze methane conversions, methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs). These enzymes have been difficult to incorporate into industrial processes due to their complexity, poor stability, and lack of recombinant tractability. Despite these issues, new ways of preparing and stabilizing these enzymes have recently been discovered, and new mechanistic insight into how MCRs and MMOs break the C-H bond in nature's most inert hydrocarbon have been obtained...
October 18, 2016: Current Opinion in Chemical Biology
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
Michael A Rogawski
Since the 1970s, racetams have been in use as cognitive enhancers. Levetiracetam was discovered to have antiseizure activity in animal models and was then found to bind to SV2A in synaptic and endocrine vesicles. Brivaracetam, an analog of levetiracetam, was identified in a medicinal chemistry campaign with the objective of discovering analogs with higher affinity at racetam-binding sites and greater antiseizure potency.
October 20, 2016: Cell
Narges Abdali, Jerry Matthew Parks, Keith Haynes, Julie L Chaney, Adam T Green, David Wolloscheck, John K Walker, Valentin V Rybenkov, Jerome Yves Baudry, Jeremy C Smith, Helen I Zgurskaya
Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for development of effective EPIs, especially in light of constantly emerging resistance. Here, we describe EPIs that interact with periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel...
October 21, 2016: ACS Infectious Diseases
Rongsheng Zhu, Zhanguo Zhang, Yang Li, Zhenbang Hu, Dawei Xin, Zhaoming Qi, Qingshan Chen
Previous studies have confirmed that there are many differences between animal and plant microRNAs (miRNAs), and that numerical features based on sequence and structure can be used to predict the function of individual miRNAs. However, there is little research regarding numerical differences between animal and plant miRNAs, and whether a single numerical feature or combination of features could be used to distinguish animal and plant miRNAs or not. Therefore, in current study we aimed to discover numerical features that could be used to accomplish this...
2016: PloS One
Christoph Nowak, Samira Salihovic, Andrea Ganna, Stefan Brandmaier, Taru Tukiainen, Corey D Broeckling, Patrik K Magnusson, Jessica E Prenni, Rui Wang-Sattler, Annette Peters, Konstantin Strauch, Thomas Meitinger, Vilmantas Giedraitis, Johan Ärnlöv, Christian Berne, Christian Gieger, Samuli Ripatti, Lars Lind, Nancy L Pedersen, Johan Sundström, Erik Ingelsson, Tove Fall
Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test...
October 2016: PLoS Genetics
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
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