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https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#1
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423635/quantification-of-her2-and-estrogen-receptor-heterogeneity-in-breast-cancer-by-single-molecule-rna-fluorescence-in-situ-hybridization
#2
Laura Annaratone, Michele Simonetti, Erik Wernersson, Caterina Marchiò, Silvano Garnerone, Maria Stella Scalzo, Magda Bienko, Roberto Chiarle, Anna Sapino, Nicola Crosetto
Intra-tumor heterogeneity is a pervasive property of human cancers that poses a major clinical challenge. Here, we describe the characterization, at the transcriptional level, of the intra-tumor topography of two prominent breast cancer biomarkers and drug targets, epidermal growth factor receptor 2 (HER2) and estrogen receptor 1 (ER) in 49 archival breast cancer samples. We developed a protocol for single-molecule RNA FISH in formalin-fixed, paraffin-embedded tissue sections (FFPE-smFISH), which enabled us to simultaneously detect and perform absolute quantification of HER2 and ER mature transcripts in single cells and multiple tumor regions...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421119/influences-of-realgar-indigo-naturalis-a-traditional-chinese-medicine-formula-on-the-main-cyp450-activities-in-rats-using-a-cocktail-method
#3
Huan-Hua Xu, Fei-Ran Hao, Mei-Xi Wang, Si-Jia Ren, Ming Li, Hong-Ling Tan, Yu-Guang Wang, Xiang-Lin Tang, Cheng-Rong Xiao, Qian-De Liang, Yue Gao, Zeng-Chun Ma
The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28416508/hus-and-atypical-hus
#4
T Sakari Jokiranta
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by shiga-toxin producing E. coli (STEC) infection, atypical HUS (aHUS), usually caused by uncontrolled complement activation, or secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical (i.e. STEC-HUS) follows a gastrointestinal infection with STEC, while aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28413720/direct-imaging-of-app-proteolysis-in-living-cells
#5
Niccoló Parenti, Ambra Del Grosso, Claudia Antoni, Marco Cecchini, Renato Corradetti, Francesco S Pavone, Martino Calamai
Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue...
2017: PeerJ
https://www.readbyqxmd.com/read/28412197/an-uplc-ms-ms-method-for-the-quantification-of-braf-inhibitors-vemurafenib-dabrafenib-and-mek-inhibitors-cobimetinib-trametinib-binimetinib-in-human-plasma-application-to-treated-melanoma-patients
#6
Marine Rousset, Karine Titier, Stephane Bouchet, Caroline Dutriaux, Anne Pham-Ledard, Sorilla Prey, Mireille Canal-Raffin, Mathieu Molimard
Targeted therapies for cancers are fast-growing therapies. For instance kinase inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are increasingly used to treat malignant melanoma. The metabolic profile of these drugs can result in great interindividual variability, justifying therapeutic drug monitoring (TDM). We describe a rapid and specific method for quantification of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with CORTECS C18+ column, under a gradient of 10% acetic acid in water/acetonitrile...
April 12, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28411632/an-ultra-specific-and-sensitive-sandwich-elisa-for-imatinib-using-two-anti-imatinib-antibodies
#7
Tetsuya Saita, Yuta Yamamoto, Kazuhisa Hosoya, Yutaro Yamamoto, Sakiko Kimura, Yutaka Narisawa, Masashi Shin
The development of an immunoassay for a low-molecular-weight drug first requires the identification of specific antibodies that do not cross-react with the drug's metabolites. If two antibodies can simultaneously recognize the entire structure of the drug, we can then utilize them to establish an ultra-specific sandwich ELISA, free from interference due to the metabolic products of the drug. This paper reports an ultra-specific and sensitive sandwich ELISA for determination of the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies...
May 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28411464/development-validation-and-different-approaches-for-the-measurement-uncertainty-of-a-multi-class-veterinary-drugs-residues-lc-ms-method-for-feeds
#8
Andressa Camargo Valese, Luciano Molognoni, Naielly Coelho de Souza, Leandro Antunes de Sá Ploêncio, Ana Carolina Oliveira Costa, Fabiano Barreto, Heitor Daguer
A sensitive method for the simultaneous residues analysis of 62 veterinary drugs in feeds by liquid chromatography-tandem mass spectrometry has been developed and validated in accordance to Commission Decision 657/2002/EC. Additionally, limits of detection (LOD), limits of quantitation (LOQ), matrix effects and measurement uncertainty were also assessed. Extraction was performed for all analytes and respective internal standards in a single step and chromatographic separation was achieved in only 12min. LOQ were set to 0...
March 25, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#9
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28398227/miniaturized-real-time-pcr-on-a-q3-system-for-rapid-kras-genotyping
#10
Maria Guarnaccia, Rosario Iemmolo, Salvatore Petralia, Sabrina Conoci, Sebastiano Cavallaro
Colorectal cancer (CRC) is an aggressive human malignancy with a complex genomic landscape harboring KRAS mutations. In 40%-60% of patients with CRC, constantly active KRAS proteins affect the prognosis, surgical strategy, and clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) agents. For this reason, there is a greater demand for minimally-invasive diagnostic devices to characterize the genetic pattern and prevent the acquired mechanism to drug resistance. The rapid developments in cutting-edge diagnostic techniques are expected to play a growing role in medicine and represent an attractive promise to identify potential responders to personalized medicine...
April 11, 2017: Sensors
https://www.readbyqxmd.com/read/28397043/simvastatin-prevents-lipopolysaccharide-induced-septic-shock-in-rats
#11
Li Yu, Xing-Wen Da, Xiao-Ling Wu, Ao-di He, Ding Long
Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28395991/simultaneous-determination-of-cocaine-crack-and-its-metabolites-in-oral-fluid-urine-and-plasma-by-liquid-chromatography-mass-spectrometry-and-its-application-in-drug-users
#12
Taís Regina Fiorentin, Felipe Bianchini D'Avila, Eloisa Comiran, Amanda Zamboni, Juliana Nichterwitz Scherer, Flavio Pechansky, Paulo Eduardo Mayorga Borges, Pedro Eduardo Fröehlich, Renata Pereira Limberger
INTRODUCTION: A single LC-MS equipment was used to validate three methods for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) in oral fluid (OF), urine and plasma. METHODS: The methods were carried out using a Kinetex HILIC column for polar compounds at 30°C. Mobile phase with isocratic condition of acetonitrile: 13mM ammonium acetate pH 6.0: methanol (55:35:10 v/v/v) at 0...
April 7, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28395244/an-isocratic-hydrophilic-interaction-liquid-chromatographic-method-for-simultaneous-determination-of-iodixanol-and-its-related-impurities-in-drug-substance
#13
Bruno D Rondon, Neila M Cassiano, Quezia B Cass
This work reports a simple isocratic hydrophilic interaction liquid chromatographic (HILIC) method for the simultaneous quantification of iodixanol and of its related impurities C, D and E in drug substance. The chromatographic separation was carried out with a Kinetex™ HILIC column, using acetonitrile and formic acid aqueous solution (1.0mmol/L, pH 3.2) (92:08, v/v) as eluent at a flow rate of 0.8mL/min. The autosampler and column temperature were maintained at 20°C and UV detection was set at 243nm. The method was validated in accordance to the ICH guideline and employed for the analysis of two different lots of iodixanol drug substance...
March 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28390021/pharmaceuticals-and-illicit-drugs-in-wastewater-samples-in-north-eastern-tunisia
#14
Bilel Moslah, Evroula Hapeshi, Amel Jrad, Despo Fatta-Kassinos, Abderrazek Hedhili
Pharmaceutically active substances (PhACs) and drugs of abuse (DAs) are two classes of contaminants of emerging concern that have attracted great concern and interest by the scientific community during the last two decades. Numerous studies have revealed their presence in treated urban wastewaters. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, and are thus able to reach the aquatic environment through wastewater discharge and reuse practices...
April 7, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28381120/simultaneous-assessment-of-the-efficacy-and-toxicity-of-marine-mollusc-derived-brominated-indoles-in-an-in-vivo-model-for-early-stage-colon-cancer
#15
Babak Esmaeelian, Kirsten Benkendorff, Richard K Le Leu, Catherine A Abbott
The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita, while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later...
April 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28374584/multiparameter-quantification-of-liposomal-nanomedicines-at-the-single-particle-level-by-high-sensitivity-flow-cytometry
#16
Chaoxiang Chen, Shaobin Zhu, Shuo Wang, Wenqiang Zhang, Yu Cheng, Xiaomei Yan
Drug-encapsulated liposomes have been considered the most clinically acceptable drug delivery systems. However, current methods fall short in the quantitative characterization of individual nanoliposomes due to their small sizes and large heterogeneity. Here we report a high-throughput method for the absolute quantification of particle size, drug content, fraction of drug encapsulation, and particle concentration of liposomal nanomedicines at the single-particle level. A laboratory-built high sensitivity flow cytometer (HSFCM) was used to simultaneously detect the side scattered and fluorescence signals generated by individual nanomedicine particles at a speed up to 10000 nanoparticles per minute...
April 4, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28371721/meropenem-levofloxacin-and-linezolid-in-human-plasma-of-critical-care-patients-a-fast-semi-automated-micro-extraction-by-packed-sorbent-uhplc-pda-method-for-their-simultaneous-determination
#17
Vincenzo Ferrone, Roberto Cotellese, Lorenzo Di Marco, Simona Bacchi, Maura Carlucci, Annadomenica Cichella, Paolo Raimondi, Giuseppe Carlucci
An ultra high-performance liquid chromatographic (UHPLC) method with PDA detection was developed and validated for the simultaneous quantification of meropenem, linezolid, and levofloxacin in human plasma and applied in human plasma of critical care patients. A semi-automated microextraction by packed sorbent (MEPS) for sample preparation was used. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration - ejection cycles) and in the desorption step (percentage of acetonitrile in the solvent of elution and number of aspirations of elution solvent through the device) were statistically significant when the recovery was used as response...
March 21, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28361525/a-rapid-validated-uv-hplc-method-for-the-simultaneous-determination-of-the-antiretroviral-compounds-darunavir-and-raltegravir-in-their-dosage-form
#18
G Estan-Cerezo, A García-Monsalve, L Soriano-Irigaray, F J Rodríguez-Lucena, A Navarro-Ruiz
OBJECTIVE: A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form. METHODS: The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5-100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15x0.4.6 cm) column at 35ºC...
March 29, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28350109/pathway-deviation-based-biomarker-and-multi-effect-target-identification-in-asbestos-related-squamous-cell-carcinoma-of-the-lung
#19
Jiang Du, Lin Zhang
Asbestos-related lung carcinoma is one of the most devastating occupational cancers, and effective techniques for early diagnosis are still lacking. In the present study, a systematic approach was applied to detect a potential biomarker for asbestos-related lung cancer (ARLC); in particular asbestos-related squamous cell carcinoma (ARLC-SCC). Microarray data (GSE23822) were retrieved from the Gene Expression Omnibus database, including 26 ARLC-SCCs and 30 non-asbestos-related squamous cell lung carcinomas (NARLC-SCCs)...
February 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28348149/pharmacokinetics-and-placental-transfer-of-elvitegravir-and-dolutegravir-and-other-antiretrovirals-during-pregnancy
#20
Bassam H Rimawi, Erica Johnson, Augustine Rajakumar, Sijia Tao, Yong Jiang, Scott Gillespie, Raymond F Schinazi, Mark Mirochnick, Martina L Badell, Rana Chakraborty
The integrase inhibitors, elvitegravir (EVG) and dolutegravir (DTG), rapidly decrease plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentration of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMC) concentrations or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood, and within placentae from HIV-1-infected pregnant women...
March 27, 2017: Antimicrobial Agents and Chemotherapy
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