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https://www.readbyqxmd.com/read/28534009/genomic-insight-into-mechanisms-of-reversion-of-antibiotic-resistance-in-multidrug-resistant-mycobacterium-tuberculosis-induced-by-a-nanomolecular-iodine-containing-complex-fs-1
#1
Aleksandr I Ilin, Murat E Kulmanov, Ilya S Korotetskiy, Rinat A Islamov, Gulshara K Akhmetova, Marina V Lankina, Oleg N Reva
Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#2
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28530711/a-combinatorial-screen-of-the-cloud-uncovers-a-synergy-targeting-the-androgen-receptor
#3
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Sara Sdelci, Erika Schirghuber, André C Müller, Michael Caldera, Anja Wagner, Rebecca Herzog, Thomas Penz, Michael Schuster, Bernd Boidol, Gerhard Dürnberger, Yasin Folkvaljon, Pär Stattin, Vladimir Ivanov, Jacques Colinge, Christoph Bock, Klaus Kratochwill, Jörg Menche, Keiryn L Bennett, Stefan Kubicek
Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC)...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#4
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28522589/identification-of-cancer-targeted-tropomyosin-inhibitors-and-their-synergy-with-microtubule-drugs
#5
Mark A Currier, Justine R Stehn, Ashleigh Swain, Duo Chen, Jeff Hook, Eleanor Eiffe, Andrew Heaton, David Brown, Brooke Nartker, David W Eaves, Nina Kloss, Herbert Treutlein, Jun Zeng, Irina B Alieva, Vera B Dugina, Edna C Hardeman, Peter W Gunning, Timothy P Cripe
Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While anti-microtubule drugs are well-established, anti-actin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other anti-tropomyosin analogues for anti-cancer and on-target activity using a series of in vitro cell-based and biochemical assays...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522584/cooperative-targets-of-combined-mtor-hdac-inhibition-promote-myc-degradation
#6
John K Simmons, Aleksandra M Michalowski, Benjamin J Gamache, Wendy DuBois, Jyoti Patel, Ke Zhang, Joy Gary, Shuling Zhang, Snehal Gaikwad, Daniel Connors, Nicholas Watson, Elena Leon, Jin-Qiu Chen, W Michael Kuehl, Maxwell P Lee, Adriana Zingone, Ola Landgren, Peter Ordentlich, Jing Huang, Beverly A Mock
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents.  In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28511381/prevalence-of-carbapenem-resistant-non-fermenting-gram-negative-bacterial-infection-and-identification-of-carbapenemase-producing-nfgnb-isolates-by-simple-phenotypic-tests
#7
Jane Esther, Diego Edwin, Uma
INTRODUCTION: Non-Fermenting Gram negative bacilli (NFGNB) are emerging multi-drug resistant pathogens causing nosocomial infections. In recent years, carbapenem resistance in NFGNB has increased due to a variety of drug resistance mechanisms, the most common being production of carbapenemases. AIM: To detect carbapenemase and metallo-β-lactamase (MBL) production in NFGNBs by four phenotypic tests and to compare the various phenotypic methods for detection of carbapenemase and MBL production in nosocomial NFGNB isolates...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507307/a-novel-indication-for-panobinostat-as-a-senolytic-drug-in-nsclc-and-hnscc
#8
Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M McDaid
Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505442/nitric-oxide-donor-based-cancer-therapy-advances-and-prospects
#9
Zhangjian Huang, Junjie Fu, Yihua Zhang
The increasing understanding of the role of nitric oxide (NO) in cancer biology has generated significant progress in the use of NO donor-based therapy to fight cancer. These advances strongly suggest the potential adoption of NO donor-based therapy in clinical practice, and this has been supported by several clinical studies in the past decade. In this review, we first highlight several types of important NO donors, including recently developed NO donors bearing a dinitroazetidine skeleton, represented by RRx-001, with potential utility in cancer therapy...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28503342/phenotypic-detection-and-antibiogram-of-%C3%AE-lactamase-producing-proteus-species-in-a-tertiary-care-hospital-india
#10
N Pal, S Hooja, R Sharma, R K Maheshwari
BACKGROUND: Proteus species cause a variety of community- and hospital-acquired illnesses. Synthesis of β-lactamases is the predominant mechanism for resistance to β-lactam antibiotics. Among the β-lactamases, extended spectrum β-lactamases (ESBLs) and AmpC β-lactamases are the most common. AIM: The objective of this study was to determine the occurrence of ESBL and AmpC β-lactamases in Proteus species among various clinical isolates at a tertiary care hospital, India...
September 2016: Annals of Medical and Health Sciences Research
https://www.readbyqxmd.com/read/28501857/combined-treatment-with-artesunate-and-bromocriptine-has-synergistic-anticancer-effects-in-pituitary-adenoma-cell-lines
#11
Xin Wang, Qiu Du, Zhigang Mao, Xiang Fan, Bin Hu, Zhen Wang, Zhiyong Chen, Xiaobing Jiang, Zongming Wang, Ni Lei, Haijun Wang, Yonghong Zhu
Prolactinomas are the most prevalent functional pituitary adenomas. The preferred treatments for prolactinomas are dopamine agonists (DAs) such as bromocriptine (BRC), but DAs still have the challenges of tumor recurrence and drug resistance. This study demonstrates that the synergy of function and mechanism between artesunate (ART) and BRC inhibits prolactinoma cell growth in vitro. We found that low-dose ART combined with BRC synergistically inhibited the growth of GH3 and MMQ cell lines, caused cell death, attenuated cell migration and invasion, and suppressed the expression of extracellular prolactin...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490008/an-uncommon-st1224-ndm-1-producing-klebsiella-pneumoniae-isolated-from-the-bloodstream-of-a-leukemia-patient-in-china
#12
Xiaoxiao Zhang, Jia Du, Cui Zhou, Jianming Cao, Hong Lu, Haiyang Liu, Wenzi Bi, Tieli Zhou
AIMS: This study aimed to analyze the clinical data and characteristics of an NDM-1 (New Delhi metallo-β-lactamase-1)-producing Klebsiella pneumoniae isolated from the bloodstream of a leukemia patient. MATERIALS AND METHODS: A retrospective analysis was used for the clinical data of the patient. The modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy test were used for detecting metallo-β-lactamase. Antibiotic resistance was determined using the agar dilution method...
May 11, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28485723/developing-gene-and-cell-therapies-for-rare-diseases-an-opportunity-for-synergy-between-academia-and-industry
#13
REVIEW
F Mavilio
For the last twenty years, academic research has been the major, and often only, driving force behind the spectacular development of gene transfer technology for the therapy of rare genetic diseases. Investors and industry became eventually interested in gene and cell therapy, due to the success of a series of pioneering clinical trials that proved efficacy and safety of last-generation technology, and to favorable orphan drug legislation in both Europe and the United States. Developing this forms of therapy is however complex and requires skills and knowledge not necessary available to the industry, which is better placed to develop processes and products and put them on the market...
May 9, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28483959/gepotidacin-gsk2140944-in-vitro-activity-against-gram-positive-and-gram-negative-bacteria-mbc-mic-kill-kinetics-checkerboard-pae-sme-tests
#14
R K Flamm, D J Farrell, P R Rhomberg, N E Scangarella-Oman, H S Sader
Gepotidacin is a first in class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the minimum inhibitory (MIC) and minimum bactericidal concentration (MBC) activity of gepotidacin and comparator agents against Staphylococcus aureusStreptococcus pneumoniae and Escherichia coli. Gepotidacin in vitro activity was also evaluated using time-kill kinetics, broth microdilution checkerboard methods for synergy testing, and for postantibiotic and subinhibitory effects...
May 8, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28482064/gut-liver-axis-and-sterile-signals-in-the-development-of-alcoholic-liver-disease
#15
Gyongyi Szabo, Jan Petrasek
Background: Innate immunity plays a critical role in the development of alcohol-induced liver inflammation. Understanding the inter-relationship of signals from within and outside of the liver that trigger liver inflammation is pivotal for development of novel therapeutic targets of alcoholic liver disease (ALD). Aim: The aim of this paper is to review recent advances in the field of alcohol-induced liver inflammation. Methods: A detailed literature review was performed using the PubMed database published between January 1980 and December 2016...
May 8, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28476069/elac-3-12-di-o-acetyl-8-o-tigloilingol-a-plant-derived-lathyrane-diterpene-induces-subventricular-zone-neural-progenitor-cell-proliferation-through-protein-kinase-c-beta-activation
#16
Maribel Murillo-Carretero, Noelia Geribaldi-Doldán, Eugenia Flores-Giubi, Francisco García-Bernal, Elkin A Navarro, Manuel Carrasco-Viñuela, Antonio J Macías-Sánchez, Pilar Herrero-Foncubierta, Antonio Delgado-Ariza, Cristina Verástegui, Jesús Domínguez-Riscart, Mourad Daoubi, Rosario Hernández-Galán, Carmen Castro
BACKGROUND AND PURPOSE: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathologic or traumatic brain lesions. We have previously shown that non-tumor-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with lathyrane skeleton can also activate PKC and promote NPC proliferation...
May 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28475767/advances-in-computational-approaches-in-identifying-synergistic-drug-combinations
#17
Zhen Sheng, Yi Sun, Zuojing Yin, Kailin Tang, Zhiwei Cao
Accumulated empirical clinical experience, supported by animal or cell line models, has initiated efforts of predicting synergistic combinatorial drugs with more-than-additive effect compared with the sum of the individual agents. Aiming to construct better computational models, this review started from the latest updated data resources of combinatorial drugs, then summarized the reported mechanism of the known synergistic combinations from aspects of drug molecular and pharmacological patterns, target network properties and compound functional annotation...
May 5, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28473769/an-introduction-to-terminology-and-methodology-of-chemical-synergy-perspectives-from-across-disciplines
#18
REVIEW
Kyle R Roell, David M Reif, Alison A Motsinger-Reif
The idea of synergistic interactions between drugs and chemicals has been an important issue in the biomedical world for over a century. As complex diseases, especially cancer, are being treated with various drug cocktails, understanding the interactions among these drugs is increasingly vital to ensuring successful treatment regimens. However, the idea of synergy is not limited to only the biomedical realm and these ideas have developed across many different disciplines, as well. In this review, we first discuss the various terminology surrounding the idea of synergy, providing a comprehensive list of terms defined across numerous disciplines...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28468774/synergy-between-androgen-receptor-antagonism-and-inhibition-of-mtor-and-her2-in-breast-cancer
#19
Michael A Gordon, Nicholas C D'Amato, Haihua Gu, Beatrice Babbs, Julia D Wulfkuhle, Emanuel F Petricoin, Isela Gallagher, Ting Dong, Kathleen Torkko, Bolin Liu, Anthony Elias, Jennifer K Richer
The androgen receptor (AR) is widely expressed in breast cancer (BC) and evidence suggests dependence on AR signaling for growth and survival. AR antagonists such as enzalutamide and seviteronel have shown success in pre-clinical models and clinical trials of prostate cancer, and are currently being evaluated in BC. Reciprocal regulation between AR and the HER2/PI3K/mTOR pathway may contribute to resistance to HER2- and mTOR-targeted therapies; thus, dual inhibition of these pathways may synergistically inhibit BC growth...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28465296/exploiting-ar-regulated-drug-transport-to-induce-sensitivity-to-the-survivin-inhibitor-ym155
#20
Michael D Nyquist, Alexandra Corella, John Burns, Ilsa Coleman, Shuai Gao, Robin Tharakan, Luke Riggan, Changmeng Cai, Eva Corey, Peter S Nelson, Elahe A Mostaghel
Androgen receptor (AR) signaling is fundamental to prostate cancer and is the dominant therapeutic target in metastatic disease. However, stringent androgen deprivation therapy regimens decrease quality of life and have been largely unsuccessful in curtailing mortality. Recent clinical and preclinical studies have taken advantage of the dichotomous ability of AR signaling to elicit growth-suppressive and differentiating effects by administering hyperphysiologic levels of testosterone. In this study, high-throughput drug screening identified a potent synergy between high-androgen therapy and YM155, a transcriptional inhibitor of survivin (BIRC5)...
May 2017: Molecular Cancer Research: MCR
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