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https://www.readbyqxmd.com/read/29334694/home-alone-a-systematic-review-and-meta-analysis-on-the-effects-of-individual-housing-on-body-weight-food-intake-and-visceral-fat-mass-in-rodents
#1
REVIEW
L Schipper, L Harvey, E M van der Beek, G van Dijk
Rats and mice are widely used to study environmental effects on psychological and metabolic health. Study designs differ widely and are often characterized by varying (social) housing conditions. In itself, housing has a profound influence on physiology and behaviour of rodents, affecting energy balance and sustainable metabolic health. However, evidence for potential long-term consequences of individual versus social housing on body weight and metabolic phenotype is inconsistent. We conducted a systematic literature review and meta-analyses assessing effects of individual versus social housing of rats and mice, living under well-accepted laboratory conditions, on measures of metabolic health, including body weight, food intake and visceral adipose tissue mass...
January 15, 2018: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#2
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334553/post-treatment-controllers-after-treatment-interruption-in-chronically-hiv-infected-patients
#3
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro
OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN: Patients were treated and monitored according to Italian guidelines...
January 13, 2018: AIDS
https://www.readbyqxmd.com/read/29334491/a-randomized-titrate-to-target-study-comparing-fixed-dose-combinations-of-azilsartan-medoxomil-and-chlorthalidone-with-olmesartan-and-hydrochlorothiazide-in-stage-2-systolic-hypertension
#4
William C Cushman, George L Bakris, William B White, Michael A Weber, Domenic Sica, Andrew Roberts, Eric Lloyd, Stuart Kupfer
BACKGROUND: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). OBJECTIVE/METHODS: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less...
January 13, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#5
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334356/p53-suppresses-mutagenic-rad52-and-pol%C3%AE-pathways-by-orchestrating-dna-replication-restart-homeostasis
#6
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks driving genomic instability genetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29334340/identification-of-anti-filarial-leads-against-aspartate-semialdehyde-dehydrogenase-of-wolbachia-endosymbiont-of-brugia-malayi-combined-molecular-docking-and-molecular-dynamics-approaches
#7
Dhamodharan Prabhu, Sundaraj Rajamanikandan, Mathimaran Amala, Surekha Kanagarajan, Jeyaraman Jeyakanthan
Lymphatic filariasis is a debilitating vector borne parasitic disease that infects human lymphatic system by nematode Brugia malayi. Currently available anti-filarial drugs are effective only on the larval stages of parasite. So far, no effective drugs are available for humans to treat filarial infections. In this regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic pathway from Wolbachia endosymbiont Brugia malayi represents an attractive therapeutic target for the development of novel anti-filarial agents...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#8
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29334299/mucoadhesive-buccal-film-containing-ornidazole-and-dexamethasone-for-oral-ulcers-in-vitro-and-in-vivo-studies
#9
Chengliang Zhang, Yanan Liu, Wei Li, Ping Gao, Dong Xiang, Xiuhua Ren, Dong Liu
A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced...
January 15, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29334287/efficacy-and-safety-of-alpha-blockers-in-medical-expulsive-therapy-for-ureteral-stones-a-mixed-treatment-network-meta-analysis-and-trial-sequential-analysis-of-randomized-controlled-clinical-trials
#10
Kannan Sridharan, Gowri Sivaramakrishnan
Alpha blockers (AB) are the main group of drugs used for medical expulsive therapy (MET) in patients with ureteral stones. However, there is no consensus on the relative efficacy and safety of individual AB in MET. Areas covered: The present work is a network meta-analysis of randomized controlled trials comparing AB with either placebo or standard of care in patients with ureteral stones. Electronic databases of Medline, Cochrane CENTRAL and Google Scholar were searched for eligible clinical studies. Inverse variance heterogeneity model was used for mixed treatment comparisons...
January 15, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#11
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29334153/heterobimetallic-complexes-for-theranostic-applications
#12
M Concepción Gimeno, Vanesa Fernández-Moreira
The design of more efficient anticancer drugs requires a deeper understanding of their biodistribution and mechanism of action. Cell imaging agents could help to gain insight into biological processes and, consequently, the best strategy for attaining suitable scaffolds in which both, biological and imaging properties are maximized. A new concept arises in this field which is the combination of two metal fragments as collaborative partners to provide the precise emissive properties to visualize the cell as well as the optimum cytotoxic activity to build more potent and selective chemotherapeutic agents...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#13
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333945/remarkable-response-with-pembrolizumab-plus-albumin-bound-paclitaxel-in-2-cases-of-her2-positive-metastatic-breast-cancer-who-have-failed-to-multi-anti-her2-targeted-therapy
#14
Bian Li, Wang Tao, Zhang Shao-Hua, Q U Ze-Rui, Jin Fu-Quan, L I Fan, Jiang Ze-Fei
In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab,lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients.Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab(2mg/Kg, day1) plus albumin-bound paclitaxel(125mg/m2, day1,8) every 3 weeks.CT evaluation and HER2 ECD test were performed every 2 cycles...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333880/pharmacogenetic-analysis-of-opioid-dependence-treatment-dose-and-dropout-rate
#15
Richard C Crist, James Li, Glenn A Doyle, Alex Gilbert, Bryan M Dechairo, Wade H Berrettini
BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. OBJECTIVES: Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). METHODS: Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68...
January 15, 2018: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/29333729/immunoengineering-with-biomaterials-for-enhanced-cancer-immunotherapy
#16
REVIEW
Yu-Qing Xie, Lixia Wei, Li Tang
Cancer immunotherapy has recently shown dramatic clinical success inducing durable response in patients of a wide variety of malignancies. Further improvement of the clinical outcome with immune related cancer treatment requests more exquisite manipulation of a patient's immune system with increased immunity against diseases while mitigating the toxicities. To meet this challenge, biomaterials applied to immunoengineering are being developed to achieve tissue- and/or cell-specific immunomodulation and thus could potentially enhance both the efficacy and safety of current cancer immunotherapies...
January 14, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29333664/increased-non-fatal-overdose-risk-associated-with-involuntary-drug-treatment-in-a-longitudinal-study-with-people-who-inject-drugs
#17
Claudia Rafful, Ricardo Orozco, Gudelia Rangel, Peter Davidson, Dan Werb, Leo Beletsky, Steffanie A Strathdee
AIM: To assess the effect of involuntary drug treatment (IDT) on non-fatal overdose among people who inject drugs (PWID). DESIGN: Longitudinal study. SETTING: Tijuana, Mexico. PARTICIPANTS: Baseline sample of 671 PWID included 258 (38.4%) women and 413 (61.6%) men. MEASUREMENTS: Primary independent variables were reported recent (i.e., past 6 months) non-fatal overdose event (dependent variable) and IDT...
January 14, 2018: Addiction
https://www.readbyqxmd.com/read/29333658/in-situ-shrna-synthesis-on-dna-polylactide-nanoparticles-to-treat-multidrug-resistant-breast-cancer
#18
Qianqian Ni, Fuwu Zhang, Yunlei Zhang, Guizhi Zhu, Zhe Wang, Zhaogang Teng, Chunyan Wang, Bryant C Yung, Gang Niu, Guangming Lu, Longjiang Zhang, Xiaoyuan Chen
Nanomedicine has shown unprecedented potential for cancer theranostics. Nucleic acid (e.g., DNA and RNA) nanomedicines are of particular interest for combination therapy with chemotherapeutics. However, current nanotechnologies to construct such nucleic acid nanomedicines, which rely on chemical conjugation or physical complexation of nucleic acids with chemotherapeutics, have restrained their clinical translation due to limitations such as low drug loading efficiency and poor biostability. Herein, in situ rolling circle transcription (RCT) is applied to synthesize short hairpin RNA (shRNA) on amphiphilic DNA-polylactide (PLA) micelles...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29333608/the-synergistic-effect-of-pdt-and-oxacillin-on-clinical-isolates-of-staphylococcus-aureus
#19
Natanel Iluz, Yasmin Maor, Natan Keller, Zvi Malik
BACKGROUND: Staphylococcus aureus is a major pathogen in clinical microbiology. It is known to cause infections at various body sites and can be life-threatening. The development of resistance to many well-established antibiotic treatments and the prevalence of methicillin-resistant S. aureus (MRAS) among hospital patients and the general community pose challenges in treating the pathogen. The antimicrobial effect of photodynamic therapy (PDT) has been a subject of study for a long time and can offer new strategies for dealing with resistant strains...
January 15, 2018: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29333596/risk-of-adverse-events-associated-with-front-line-anti-myeloma-treatment-in-medicare-patients-with-multiple-myeloma
#20
Ying Chen, David R Lairson, Wenyaw Chan, Xianglin L Du
This study aims to examine the risks of adverse events associated with anti-multiple myeloma (MM) therapies in a large population-based cohort of elderly patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and receiving anti-MM therapy were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. We compared safety outcomes between novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and other therapies and between PI- or IMiD-based regimens and PI plus IMiD combination regimens...
January 15, 2018: Annals of Hematology
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