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https://www.readbyqxmd.com/read/28337955/examining-the-in-vitro-efficacy-of-the-iap-antagonist-birinapant-as-a-single-agent-or-in-combination-with-dacarbazine-to-induce-melanoma-cell-death
#1
Vesna Vetma, Jan Rožanc, Emilie M Charles, Christian T Hellwig, Leonidas G Alexopoulos, Markus Rehm
Antagonists of inhibitor of apoptosis proteins (IAPs), alone or in combination with genotoxic therapeutics, have been shown to efficiently induce cell death in various solid tumours. The IAP antagonist birinapant is currently being tested in phase II clinical trials. We herein aimed to investigate the in vitro anti-tumour efficacy of dacarbazine, both as a single agent and in combination with birinapant, in melanoma cell lines. Covering clinically relevant drug concentration ranges, we conducted a total of 5400 measurements in a panel of 12 human melanoma cell lines representing different stages of disease progression...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28333342/activity-of-faropenem-with-and-without-rifampicin-against-mycobacterium-tuberculosis-evaluation-in-a-whole-blood-bactericidal-activity-trial
#2
Meera Gurumurthy, Rupangi Verma, Claire M Naftalin, Kim Hor Hee, Qingshu Lu, Kin Hup Tan, Simi Issac, Wenwei Lin, Angelia Tan, Kok-Yong Seng, Lawrence Soon-U Lee, Nicholas I Paton
Background: Faropenem has in vitro activity against Mycobacterium tuberculosis (Mtb) and shows synergy with rifampicin. We tested this in a whole-blood bactericidal activity (WBA) trial. Methods: We randomized healthy volunteers to receive a single oral dose of faropenem (600 mg) with amoxicillin/clavulanic acid (500/125 mg) ( n  =   8), rifampicin (10 mg/kg) ( n  =   14) or the combination rifampicin + faropenem + amoxicillin/clavulanic acid ( n  =   14)...
March 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332528/drug-discovery-crispr-finds-drug-synergy
#3
(no author information available yet)
No abstract text is available yet for this article.
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28327498/activity-of-sulfa-drugs-and-their-combinations-against-stationary-phase-b-burgdorferi-in-vitro
#4
Jie Feng, Shuo Zhang, Wanliang Shi, Ying Zhang
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B...
March 22, 2017: Antibiotics
https://www.readbyqxmd.com/read/28324660/single-and-combination-drug-screening-with-aqueous-biphasic-tumor-spheroids
#5
Pradip Shahi Thakuri, Hossein Tavana
Spheroids of cancer cells represent a physiologic model of solid tumors for cancer drug screening. Despite this known benefit, difficulties with generating large quantities of uniformly sized spheroids in standard plates, individually addressing spheroids with drug compounds, and quantitatively analyzing responses of cancer cells have hindered the use of spheroids in high-throughput screening applications. Recently, we addressed this challenge by using an aqueous two-phase system technology to generate a spheroid within an aqueous drop immersed in a second, immiscible aqueous phase...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#6
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28318525/psoriasis-and-nonalcoholic-fatty-liver-disease
#7
J M Carrascosa, C Bonanad, E Dauden, R Botella, A Olveira-Martín
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment...
March 16, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28289911/transcriptomics-as-a-tool-to-discover-new-antibacterial-targets
#8
REVIEW
Ángel Domínguez, Elisa Muñoz, M Carmen López, Miguel Cordero, José Pedro Martínez, Miguel Viñas
The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls...
March 13, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28283653/antibody-drug-conjugates-bearing-pyrrolobenzodiazepine-or-tubulysin-payloads-are-immunomodulatory-and-synergize-with-multiple-immunotherapies
#9
Jonathan Rios-Doria, Jay Harper, Raymond Rothstein, Leslie Wetzel, Jon Chesebrough, Allison M Marrero, Cui Chen, Patrick Strout, Kathy Mulgrew, Kelly A McGlinchey, Ryan Fleming, Binyam Bezabeh, John Meekin, David Stewart, Maureen Kennedy, Philip Martin, Andrew Buchanan, Nazzareno Dimasi, Emil F Michelotti, Robert E Hollingsworth
Immunogenic cell death (ICD) is the process by which certain cytotoxic drugs induce apoptosis of tumor cells in a manner that stimulates the immune system. In this study, we investigated whether antibody-drug conjugates (ADC) conjugated with pyrrolobenzodiazepine dimer (PBD) or tubulysin payloads induce ICD, modulate the immune microenvironment, and could combine with IO drugs to enhance antitumor activity. We show that these payloads on their own induced an immune response that prevented the growth of tumors following subsequent tumor cell challenge...
March 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28264618/assessment-of-early-combination-effects-of-colistin-and-meropenem-against-pseudomonas-aeruginosa-and-acinetobacter-baumannii-in-dynamic-time-kill-experiments
#10
Thomas Tängdén, Matti Karvanen, Lena E Friberg, Inga Odenholt, Otto Cars
BACKGROUND: In view of the paucity of clinical evidence, in vitro studies are needed to find antibiotic combinations effective against multidrug-resistant Gram-negative bacteria. Interpretation of in vitro effects is usually based on bacterial growth after 24 h in time-kill and checkerboard experiments. However, the clinical relevance of the effects observed in vitro is not established. In this study we explored alternative output parameters to assess the activities of colistin and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii...
March 6, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28264055/enhancement-of-pomalidomide-anti-tumor-response-with-acy-241-a-selective-hdac6-inhibitor
#11
Brian J North, Ingrid Almeciga-Pinto, David Tamang, Min Yang, Simon S Jones, Steven N Quayle
Thalidomide-based Immunomodulatory Drugs (IMiDs®), including lenalidomide and pomalidomide, are effective therapeutics for multiple myeloma. These agents have been approved with, or are under clinical development with, other targeted therapies including proteasome inhibitors, αCD38 monoclonal antibodies, as well as histone deacetylase (HDAC) inhibitors for combination therapy. HDAC inhibitors broadly targeting Class I and IIb HDACs have shown potent preclinical efficacy but have frequently demonstrated an undesirable safety profile in combination therapy approaches in clinical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28263303/pentamidine-sensitizes-gram-negative-pathogens-to-antibiotics-and-overcomes-acquired-colistin-resistance
#12
Jonathan M Stokes, Craig R MacNair, Bushra Ilyas, Shawn French, Jean-Philippe Côté, Catrien Bouwman, Maya A Farha, Arthur O Sieron, Chris Whitfield, Brian K Coombes, Eric D Brown
The increasing use of polymyxins(1) in addition to the dissemination of plasmid-borne colistin resistance threatens to cause a serious breach in our last line of defence against multidrug-resistant Gram-negative pathogens, and heralds the emergence of truly pan-resistant infections. Colistin resistance often arises through covalent modification of lipid A with cationic residues such as phosphoethanolamine-as is mediated by Mcr-1 (ref. 2)-which reduce the affinity of polymyxins for lipopolysaccharide(3). Thus, new strategies are needed to address the rapidly diminishing number of treatment options for Gram-negative infections(4)...
March 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28257943/photodynamic-therapy-enhances-the-efficacy-of-gene-directed-enzyme-prodrug-therapy
#13
Catherine Christie, Aftin Pomeroy, Rohit Nair, Kristian Berg, Henry Hirschberg
INTRODUCTION: Gene-directed enzyme prodrug therapy (GDEPT) employing the cytosine deaminase (CD) gene, which encodes an enzyme that converts the nontoxic agent 5-fluorocytosine (5-FC) into the chemotherapeutic drug 5-fluorouracil (5-FU), has shown promise both in experimental animals and in clinical trials. Nevertheless, with the transfection systems available presently the percentage of tumor cells incorporating the desired gene is usually too low for successful therapy. We have examined the ability of photodynamic therapy (PDT) to enhance the efficacy of the metabolites, converted from 5-FC by CD gene transfected rat glioma cells...
February 28, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28257903/does-a-triple-combination-have-better-activity-than-double-combinations-against-multiresistant-fungi-experimental-in-vitro-evaluation
#14
Adela Martin-Vicente, Josep Guarro, Javier Capilla
In this study, the in vitro interactions of amphotericin B (AmB), voriconazole (VRC) and anidulafungin (AFG) in double and triple combinations against four species of multiresistant fungi (Fusarium solani, Lomentospora prolificans, Scopulariopsis brevicaulis and Scopulariopsis brumptii) were evaluated. In general, AmB combined with AFG was the most synergistic, especially against F. solani (7/8; 87.5%) when low concentrations of AmB were used, i.e. 0.125-0.5 µg/mL. The least active combination was AmB + VRC, with the lowest percentage of synergy against S...
February 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28255602/combination-of-thioridazine-and-dicloxacillin-as-a-possible-treatment-strategy-of-staphylococci
#15
Kristian Severin Rasmussen, Marianne Ø Poulsen, Kirstine Jacobsen, Marianne N Skov, Hans Jørn Kolmos, Birgitte H Kallipolitis, Janne K Klitgaard
We have previously shown that the phenothiazine, thioridazine, acts in synergy with the beta-lactam antibiotic, dicloxacillin, to kill methicillin-resistant Staphylococcus aureus. In this study, we investigated whether synergy by combining these two drugs could also be observed in vancomycin intermediate susceptible S. aureus (VISA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Synergy was observed in three of four tested VISA strains, suggesting that the thickening of cell wall does not interfere with the effects of thioridazine...
March 1, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28249781/assessment-of-anti-cancerous-potential-of-6-gingerol-tongling-white-ginger-and-its-synergy-with-drugs-on-human-cervical-adenocarcinoma-cells
#16
Fang Zhang, Jian-Guo Zhang, Jie Qu, Qi Zhang, Chandan Prasad, Zhao-Jun Wei
The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 μM) and IC80 (133.01 μM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells...
February 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#17
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28245622/synergy-effects-in-the-chemical-synthesis-and-extensions-of-multicomponent-reactions-mcrs-the-low-energy-way-to-ultra-short-syntheses-of-tailor-made-molecules
#18
REVIEW
Heiner Eckert
Several novel methods, catalysts and reagents have been developed to improve organic synthesis. Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multicomponent reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with 'classical' two-component reactions, fulfilling the rules of Green Chemistry. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-cost materials, drugs and compound libraries...
February 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28236033/co-targeting-the-her-and-igf-insulin-receptor-axis-in-breast-cancer-with-triple-targeting-with-endocrine-therapy-for-hormone-sensitive-disease
#19
Ashok Chakraborty, Christos Hatzis, Michael P DiGiovanna
PURPOSE: Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor)...
February 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28235402/anti-mycobacteria-potential-and-synergistic-effects-of-combined-crude-extracts-of-selected-medicinal-plants-used-by-bapedi-traditional-healers-to-treat-tuberculosis-related-symptoms-in-limpopo-province-south-africa
#20
Nancy Patience Motlalepula Komape, Victor Patrick Bagla, Prudence Kabongo-Kayoka, Peter Masoko
BACKGROUND: Tuberculosis is an infectious communicable disease and the causative agent of the disease has over the years developed resistance to streamline chemotherapeutic agents with dire consequences and there is a need for development of new and more potent alternatives. METHODS: Constituents of leaves material of Combretum heroroense, Citrus lemon and Apodytes dimidiata were serially extracted using solvents of varying polarity. TLC finger print profile of the different extracts were determined by spraying eluted plates with vanillin sulphuric acid and 2, 2- diphenylpicryl hydrazyl (DPPH) for the presence of antioxidant constituents...
February 24, 2017: BMC Complementary and Alternative Medicine
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