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https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#1
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29136623/synergistic-effect-of-eicosapentaenoic-acid-on-antiproliferative-action-of-anticancer-drugs-in-a-cancer-cell-line-model
#2
Ayako Ogo, Sachi Miyake, Hisako Kubota, Masaharu Higashida, Hideo Matsumoto, Fusako Teramoto, Toshihiro Hirai
BACKGROUND/AIMS: It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. METHODS: EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors...
November 14, 2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29136155/a-model-informed-preclinical-approach-for-prediction-of-clinical-pharmacodynamic-interactions-of-anti-tb-drug-combinations
#3
Oskar Clewe, Sebastian G Wicha, Corné P de Vogel, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
Background: Identification of pharmacodynamic interactions is not reasonable to carry out in a clinical setting for many reasons. The aim of this work was to develop a model-informed preclinical approach for prediction of clinical pharmacodynamic drug interactions in order to inform early anti-TB drug development. Methods: In vitro time-kill experiments were performed with Mycobacterium tuberculosis using rifampicin, isoniazid or ethambutol alone as well as in different combinations at clinically relevant concentrations...
November 9, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29131824/predictive-model-identifies-key-network-regulators-of-cardiomyocyte-mechano-signaling
#4
Philip M Tan, Kyle S Buchholz, Jeffrey H Omens, Andrew D McCulloch, Jeffrey J Saucerman
Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration. The model identifies calcium, actin, Ras, Raf1, PI3K, and JAK as key regulators of cardiac mechano-signaling and characterizes crosstalk logic imparting differential control of transcription by AT1R, integrins, and calcium channels...
November 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29129512/thieno-2-3-b-pyridine-derivatives-are-potent-anti-platelet-drugs-inhibiting-platelet-activation-aggregation-and-showing-synergy-with-aspirin
#5
Naif K Binsaleh, Catherine A Wigley, Kathryn A Whitehead, Michelle van Rensburg, Johannes Reynisson, Lisa I Pilkington, David Barker, Sarah Jones, Nina C Dempsey-Hibbert
Drugs which inhibit platelet function are commonly used to prevent blood clot formation in patients with Acute Coronary Syndromes (ACS) or those at risk of stroke. The thieno[3,2-c]pyridine class of therapeutic agents, of which clopidogrel is the most commonly used, target the P2Y12 receptor, and are often used in combination with acetylsalicylic acid (ASA). Six thieno[2,3-b]pyridine were assessed for in vitro anti-platelet activity; all derivatives showed effects on both platelet activation and aggregation, and showed synergy with ASA...
November 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29128840/effect-of-enrofloxacin-on-the-proteome-of-earthworms
#6
Xiaoxu Lu, Yinsheng Li, Michelle Thunders, Cory Matthew, Xiuhong Wang, Xiaojie Ai, Xinchu Zhou, Jiangping Qiu
The environmental and human health risks of veterinary drugs are becoming public health issues. Enrofloxacin (EF) is an extensively used animal-specific antibacterial agent that leaves drug residues in the environment. This study investigated the proteomic response of the earthworm Eisenia fetida to EF exposure. Earthworms were exposed to EF in soil at 1-500mg·kg(-1), and samples were collected at intervals during a 28 day period. The extracted proteins were separated by two dimensional electrophoresis to detect differentially expressed proteins (DEPs) in EF-exposed earthworms...
November 9, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29113740/efficacy-of-pritelivir-and-acyclovir-in-the-treatment-of-herpes-simplex-virus-infections-in-a-mouse-model-of-herpes-simplex-encephalitis
#7
Debra C Quenelle, Alexander Birkmann, Thomas Goldner, Tamara Pfaff, Holger Zimmermann, Susanne Bonsmann, Deborah J Collins, Terri L Rice, Mark N Prichard
Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30 mg/kg reduced mortality (P < 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3 mg/kg increased survival (P < 0...
November 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29108951/automated-time-lapse-microscopy-a-novel-method-for-screening-of-antibiotic-combination-effects-against-multidrug-resistant-gram-negative-bacteria
#8
Wanchana Ungphakorn, Pernilla Lagerbäck, Elisabet I Nielsen, Thomas Tängdén
OBJECTIVES: Antibiotic combinations are often used for carbapenemase-producing Enterobacteriaceae (CPE) but more data are needed on the optimal selection of drugs. This study aimed to evaluate the feasibility of a novel automated method based on time-lapse microscopy (the oCelloScope, Philips BioCell A/S, Allerød, Denmark) to determine in vitro combination effects against CPE and to discuss advantages and limitations of the oCelloScope in relation to standard methods. METHODS: Four Klebsiella pneumoniae and two Escherichia coli were exposed to colistin, meropenem, rifampin and tigecycline, alone and in combination...
November 3, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29100024/towards-repositioning-of-quinacrine-for-treatment-of-acute-myeloid-leukemia-promising-synergies-and-in-vivo-effects
#9
Anna Eriksson, Efthymia Chantzi, Mårten Fryknäs, Joachim Gullbo, Peter Nygren, Mats Gustafsson, Martin Höglund, Rolf Larsson
We previously reported that the anti-malarial drug quinacrine has potential to be repositioned for treatment of acute myeloid leukemia (AML). As a next step towards clinical use, we assessed the efficacy of quinacrine in an AML-PS mouse model and investigated possible synergistic effects when combining quinacrine with nine other antileukemic compounds in two AML cell lines. Furthermore, we explored the in vivo activity of quinacrine in combination with the widely used AML agent cytarabine. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST)...
October 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096687/synergistic-effects-of-combining-proteasome-inhibitors-with-chemotherapeutic-drugs-in-lung-cancer-cells
#10
Linda Sooman, Joachim Gullbo, Michael Bergqvist, Stefan Bergström, Johan Lennartsson, Simon Ekman
BACKGROUND: The prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients...
November 2, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29089766/evaluation-of-synergistic-osteogenesis-between-icariin-and-bmp2-through-a-micro-meso-hierarchical-porous-delivery-system
#11
Qian Wang, Lingyan Cao, Yang Liu, Ao Zheng, Jiannan Wu, Xinquan Jiang, Ping Ji
BMP2 is well known as an outstanding growth factor for inducing new bone formation. However, improvements are still required to use BMP2 effectively and expand its clinical application due to the potential side effects at high doses. In this study, icariin (IC), a type of traditional Chinese medicine, was originally proposed to be a cooperative factor for BMP2. An alkaline phosphatase (ALP) activity assay showed that IC promoted BMP2 osteogenesis in a concentration-dependent manner with significant enhancement at 38...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29078351/albendazole-and-antibiotics-synergize-to-deliver-short-course-anti-wolbachia-curative-treatments-in-preclinical-models-of-filariasis
#12
Joseph D Turner, Raman Sharma, Ghaith Al Jayoussi, Hayley E Tyrer, Joanne Gamble, Laura Hayward, Richard S Priestley, Emma A Murphy, Jill Davies, David Waterhouse, Darren A N Cook, Rachel H Clare, Andrew Cassidy, Andrew Steven, Kelly L Johnston, John McCall, Louise Ford, Janet Hemingway, Stephen A Ward, Mark J Taylor
Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29074485/animal-models-of-chemotherapy-induced-mucositis-translational-relevance-and-challenges
#13
Per T Sangild, René Liang Shen, Peter Erik Lotko Pontoppidan, Mathias Rathe
Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g. GIT) insights, standardized, clinically-relevant treatment regimens and discovery of new biomarkers...
October 26, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29069576/novel-combination-of-histone-methylation-modulators-with-therapeutic-synergy-against-acute-myeloid-leukemia-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Shijun Wen, Jiankang Wang, Panpan Liu, Yiqing Li, Wenhua Lu, Yumin Hu, Jinyun Liu, Zhiyuan He, Peng Huang
Acute myeloid leukemia (AML) is a hematological malignancy with rapid disease progression and often becomes lethal without treatment. Development of effective new therapies is essential to improve the clinical outcome of AML patients. Enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) play important roles in epigenetic regulation and their altered expressions have been observed in cancer. Although EZH2 and LSD1 have opposite histone methylation functions, we found that both enzymes were paradoxically up-regulated in AML cells...
October 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29069427/use-of-genetic-and-chemical-synthetic-lethality-as-probes-of-complexity-in-bacterial-cell-systems
#15
Kristina Klobucar, Eric D Brown
Different conditions and genomic contexts are known to have an impact on gene essentiality and interactions. Synthetic lethal interactions occur when a combination of perturbations, either genetic or chemical, result in a more profound fitness defect than expected based on the effect of each perturbation alone. Synthetic lethality in bacterial systems has long been studied, however during the past decade, the emerging fields of genomics and chemical genomics have led to an increase in the scale and throughput of these studies...
October 24, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/29063088/a-metabolite-of-nobiletin-4-demethylnobiletin-and-atorvastatin-synergistically-inhibits-human-colon-cancer-cell-growth-by-inducing-g0-g1-cell-cycle-arrest-and-apoptosis
#16
Xian Wu, Mingyue Song, Peiju Qiu, Fang Li, Minqi Wang, Jinkai Zheng, Qi Wang, Fei Xu, Hang Xiao
Combining different chemopreventive agents is a promising strategy to reduce cancer incidence and mortality due to potential synergistic interactions between these agents. Previously, we demonstrated that oral administration of nobiletin (NBT, a citrus flavonoid) at 0.05% (w/w, in diet) together with atorvastatin (ATST, a lipid-lowering drug) at 0.02% (w/w, in diet) produced much stronger inhibition against colon carcinogenesis in rats in comparison with that produced by NBT (at 0.1% w/w in diet) or ATST (at 0...
October 24, 2017: Food & Function
https://www.readbyqxmd.com/read/29061761/antileishmanial-efficacy-and-pharmacokinetics-of-db766-azole-combinations
#17
April C Joice, Sihyung Yang, Abdelbasset A Farahat, Heidi Meeds, Mei Feng, Junan Li, David W Boykin, Michael Zhuo Wang, Karl A Werbovetz
Given the limitations of current antileishmanial drugs and the utility of oral combination therapy for other infections, developing an oral combination against visceral leishmaniasis should be a high priority. In vitro combination studies with DB766 and antifungal azoles against intracellular L. donovani showed that posaconazole and ketoconazole, but not fluconazole, enhanced DB766 potency. Pharmacokinetic analysis of DB766-azole combinations in uninfected Swiss Webster mice revealed that DB766 exposure was increased by higher posaconazole and ketoconazole doses, while DB766 decreased ketoconazole exposure...
October 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29061656/synergistic-antiproliferative-activity-of-the-rad51-inhibitor-ibr2-with-inhibitors-of-receptor-tyrosine-kinases-and-microtubule-protein
#18
Peter J Ferguson, Mark D Vincent, James Koropatnick
Although cancer cell genetic instability contributes to characteristics that mediate tumorigenicity, it also contributes to the tumor-selective toxicity of some chemotherapy drugs. This "synthetic lethality" can be enhanced by inhibitors of DNA repair. To exploit this potential "Achilles heel", we tested the ability of a RAD51 inhibitor to potentiate the cytotoxicity of chemotherapy drugs. 2-(benzylsulfonyl)-1-(1H-indol-3-yl)-1,2-dihydroisoquinoline (IBR2) inhibits RAD51-mediated DNA double-strand break repair but also enhances cytotoxicity of the Bcr-Abl inhibitor imatinib...
October 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29055231/correcting-cftr-folding-defects-by-small-molecule-correctors-to-cure-cystic-fibrosis
#19
REVIEW
Marjolein Mijnders, Bertrand Kleizen, Ineke Braakman
Pharmacological intervention to treat the lethal genetic disease cystic fibrosis has become reality, even for the severe, most common folding mutant F508del CFTR. CFTR defects range from absence of the protein, misfolding that leads to degradation rather than cell-surface localization (such as F508del), to functional chloride-channel defects on the cell surface. Corrector and potentiator drugs improve cell-surface location and channel activity, respectively, and combination therapy of two correctors and a potentiator have shown synergy...
October 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29053257/orthogonal-screening-of-anticancer-drugs-using-an-open-access-microfluidic-tissue-array-system
#20
Dongguo Lin, Peiwen Li, Jinqiong Lin, Bowen Shu, Weixin Wang, Qiong Zhang, Na Yang, Dayu Liu, Banglao Xu
Screening for potential drug combinations presents significant challenges to the current microfluidic cell culture systems, due to the requirement of flexibility in liquid handling. To overcome this limitation, we present here an open-access microfluidic tissue array system specifically designed for drug combination screening. The microfluidic chip features a key structure in which a nanoporous membrane is sandwiched by a cell culture chamber array layer and a corresponding media reservoir array layer. The microfluidic approach takes advantage of the characteristics of the nanoporous membrane: on one side, this membrane permits the flow of air but not liquid, thus acting as a flow-stop valve to enable automatic cell distribution; on the other side, it allows diffusion-based media exchange and thus mimics the endothelial layer...
October 31, 2017: Analytical Chemistry
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