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Drug synergy

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https://www.readbyqxmd.com/read/28420117/metabolomic-profiling-of-the-synergistic-effects-of-melittin-in-combination-with-cisplatin-on-ovarian-cancer-cells
#1
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin-Kyu Park, Jong-Woon Jeon, Valerie A Ferro, David G Watson
Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells...
April 14, 2017: Metabolites
https://www.readbyqxmd.com/read/28418907/bh3-mimetics-and-bet-inhibitors-elicit-enhanced-lethality-in-malignant-glioma
#2
Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Marc-Eric Halatsch, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Drug combination therapies remain pivotal for the treatment of heterogeneous malignancies, such as glioblastomas. Here, we show a novel lethal interaction between Bcl-xL and c-myc inhibition accomplished by bromodomain protein inhibitors. Established, patient-derived xenograft and stem cell-like glioma cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015, along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and mechanistic studies...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416645/performance-stability-of-silicon-oxide-coated-plastic-parenteral-vials
#3
Christopher M Weikart, Carlo G Pantano, Jeff R Schallenberger
A new packaging system was developed for parenteral pharmaceuticals that combines the best attributes of plastic and glass without their respective drawbacks. This technological advancement is based on the synergy between high precision injection-molded plastics and plasma coating technology. The result is a shatter resistant, optically clear, low particulate and chemically durable packaging system. The demand for this product is driven by the expanding market, regulatory constraints and product recalls for injectable drugs and biologics packaged in traditional glass materials...
April 17, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28416558/in-vitro-discordance-with-in-vivo-activity-humanized-exposures-of-ceftazidime-avibactam-aztreonam-and-tigecycline-alone-and-in-combination-against-new-delhi-metallo-%C3%AE-lactamase-producing-klebsiella-pneumoniae-in-a-murine-lung-infection-model
#4
M L Monogue, L M Abbo, R Rosa, J F Camargo, O Martinez, R A Bonomo, D P Nicolau
The management of infections with New Delhi Metallo-beta-lactamase-1 (NDM) producing bacteria remains clinically challenging given the multi-drug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM+ Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against a MDR K. pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in > 2 log10CFU bacterial reduction, therefore, no in vivo synergy was observed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28414916/quercetin-remodels-the-tumor-microenvironment-to-improve-the-permeation-retention-and-antitumor-effects-of-nanoparticles
#5
Kaili Hu, Lei Miao, Tyler J Goodwin, Jun Li, Qi Liu, Leaf Huang
Our previous work has demonstrated that Wnt16 expression in cisplatin-damaged tumor associated fibroblasts is a key factor contributing to cisplatin-resistance in malignancies. Natural anti-fibrotic compounds with low toxicities are promising candidates to downregulate Wnt16 expression, improving the antitumor effect of cisplatin nanoparticles. Upon screening several natural chemicals, we found a dietary flavonoid, quercetin, significantly suppresses Wnt16 expression in activated fibroblast. To facilitate drug delivery, we have prepared a targeted Lipid/Calcium/Phosphate nanoparticle formulation consisting of a prodrug of quercetin, i...
April 17, 2017: ACS Nano
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#6
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/28404975/mdm2-antagonists-synergize-with-pi3k-mtor-inhibition-in-well-differentiated-dedifferentiated-liposarcomas
#7
Audrey Laroche, Vanessa Chaire, Marie-Paule Algeo, Marie Karanian, Benjamin Fourneaux, Antoine Italiano
BACKGROUND: Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) are characterized by a consistent amplification of the MDM2 gene. The PI3K/AKT/mTOR pathway has been suggested to play also an important role in their tumorigenesis. Our goal was to determine whether combined MDM2 and PI3K/AKT/mTOR targeting is associated with higher anti-tumor activity than single agent alone in preclinical models of WDLPS/DDLPS. METHODS: WDLPS/DDLPS cells were exposed to RG7388 (MDM2 antagonist) and BEZ235 (PI3K/mTOR dual inhibitor) after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401005/chk1-inhibition-potentiates-the-therapeutic-efficacy-of-parp-inhibitor-bmn673-in-gastric-cancer
#8
Yuping Yin, Qian Shen, Peng Zhang, Ruikang Tao, Weilong Chang, Ruidong Li, Gengchen Xie, Weizhen Liu, Lihong Zhang, Prabodh Kapoor, Shumei Song, Jaffer Ajani, Gordon B Mills, Jianying Chen, Kaixiong Tao, Guang Peng
Globally, gastric cancer is the second leading cause of cancer deaths because of the lack of effective treatments for patients with advanced tumors when curative surgery is not possible. Thus, there is an urgent need to identify molecular targets in gastric cancer that can be used for developing novel therapies and prolonging patient survival. Checkpoint kinase 1 (Chk1) is a crucial regulator of cell cycle transition in DNA damage response (DDR). In our study, we report that Chk1 plays an important role in promoting gastric cancer cell survival and growth, which serves as an effective therapeutic target in gastric cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28399372/a-tobramycin-vector-enhances-synergy-and-efficacy-of-efflux-pump-inhibitors-against-multidrug-resistant-gram-negative-bacteria
#9
Xuan Yang, Sudeep Goswami, Bala Kishan Gorityala, Ronald Domalaon, Yinfeng Lyu, Ayush Kumar, George G Zhanel, Frank M Schweizer
Drug efflux mechanisms interact synergistically with the outer membrane permeability barrier of Gram-negative bacteria leading to intrinsic resistance that presents a major challenge for antibiotic drug development. Efflux pump inhibitors (EPIs) which block the efflux of antibiotics synergize antibiotics but the clinical development of EPI/antibiotic combination therapy to treat multidrug-resistant (MDR) Gram-negative infections has been challenging. This is in part caused by the inefficiency of current EPIs to penetrate the outer membrane and resist efflux...
April 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28398220/antibiotic-loaded-mos-sub-2-sub-nanosheets-to-combat-bacterial-resistance-via-biofilms-inhibition
#10
Xu Zhang, Wentao Zhang, Lizhi Liu, Mei Yang, Lunjie Huang, Kai Chen, Rong Wang, Baowei Yang, Daohong Zhang, Jianlong Wang
The emergence of antibiotic resistance has resulted in an increasing difficulty treating clinical infections associated with biofilms formation, one of the key processes contributed to enhance antibiotic resistance in return. With the rapid development of nanotechnology, a new way to overcome antibiotic resistance was opened up. Based on multiple properties especially antibacterial potential of MoS<sub>2</sub> nanosheets that have aroused wide attention, herein, a novel antimicrobial agent to combat resistant gram-positive <i>Staphylococcus aureus (S...
April 11, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28396359/multifunctional-telodendrimer-nanocarriers-restore-synergy-of-bortezomib-and-doxorubicin-in-ovarian-cancer-treatment
#11
Lili Wang, Changying Shi, Forrest A Wright, Dandan Guo, Xu Wang, Dongliang Wang, Richard J H Wojcikiewicz, Juntao Luo
We have developed multifunctional nanoparticles (NP) for co-delivery of bortezomib (BTZ) and doxorubicin (DOX) to synchronize their pharmacokinetic profiles and synergize their activities in solid tumor treatment, a need still unmet in the clinic. Micellar NP was formed by a spatially segregated, linear-dendritic telodendrimer containing three segments: a hydrophilic polyethylene glycol (PEG), a BTZ-conjugating intermediate, and a dendritic DOX-affinitive interior. BTZ-conjugated telodendrimers, together with DOX, self-assembled into monodispersed micelles (NP(BTZ-DOX)) with small particle sizes (20~30 nm) for dual drug delivery...
April 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28396244/enhanced-release-of-poorly-water-soluble-drugs-from-synergy-between-mesoporous-magnesium-carbonate-and-polymers
#12
Jiaojiao Yang, Caroline Alvebratt, Peng Zhang, Teresa Zardán Gómez de la Torre, Maria Strømme, Christel A S Bergström, Ken Welch
The need to combat poor water solubility has increased interest in supersaturating drug delivery systems. In this study, amorphous mesoporous magnesium carbonate (MMC) was used as a drug carrier to achieve supersaturation of tolfenamic acid and rimonabant, two drug compounds with low aqueous solubility. The potential synergy between MMC and hydroxypropyl methylcellulose (HPMC), a polymer commonly included as a precipitation inhibitor in drug delivery systems, was explored with the aim of extending the time that high supersaturation levels were maintained...
April 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28393429/lack-of-analgesic-synergy-of-the-cholecystokinin-receptor-antagonist-proglumide-and-spinal-cord-stimulation-for-the-treatment-of-neuropathic-pain-in-rats
#13
Shinsuke Inoue, Lisa M Johanek, Kathleen A Sluka
OBJECTIVE: Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS)...
April 10, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28388767/treatment-of-coronary-artery-disease-randomized-trials-on-myocardial-revascularization-and-complete-arterial-bypass-grafting
#14
Ardawan J Rastan
Friedrich Wilhelm Mohr from the very beginning of his career as a cardiac surgeon was involved in the refinements of coronary artery bypass grafting (CABG). At the Leipzig Heart Center, his spirit of early adapting to new technologies inspired the entire team and led to a matchless scientific atmosphere to find solutions to improve almost all fields of cardiac surgery, including CABG. In combination with a tremendous number of patients with indications for isolated coronary artery bypass Prof. Mohr as the surgical principle investigator and the Leipzig Heart Center were able to include patients in the Synergy between PCI [percutaneous coronary intervention] with Taxus and Cardiac Surgery (SYNTAX) trial, the first randomized trials comparing CABG and PCIs using the drug-eluting stents...
April 2017: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/28385023/impact-of-a-pharmacy-based-transitional-care-program-on-hospital-readmissions
#15
Weiyi Ni, Danielle Colayco, Jonathan Hashimoto, Kevin Komoto, Chandrakala Gowda, Bruce Wearda, Jeffrey McCombs
OBJECTIVES: Avoidable readmissions of patients discharged from hospitals are a major concern. This study evaluates the impact of pharmacist-provided postdischarge services on hospital readmissions for members of a US managed Medicaid health plan. STUDY DESIGN: Prospective cohort study. METHODS: Synergy Pharmacy Solutions (SPS) initiated a transition of care (TOC) service for high-risk members of the Kern Health Systems (KHS) managed Medicaid plan...
March 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28383902/prediction-of-antibiotic-interactions-using-descriptors-derived-from-compound-molecular-structure
#16
Daniel J Mason, Ian P Stott, Stephanie Kay Ashenden, Zohar B Weinstein, Idil Karakoc, Selin Meral, Nurdan Kuru, Andreas Bender, Murat Cokol
Combination antibiotic therapies are clinically important in the fight against bacterial infections, especially when infectious agent is resistant to single antibiotics. However, the search-space of drug combinations is large, making the identification of effective combinations a challenging task. Here, we present a computational framework that uses substructure profiles derived from drug molecular structures and predicts synergistic, additive, or antagonistic antibiotic combinations. We developed our model in a previously published data set of 153 drug pairs...
April 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28379424/combination-therapy-with-potent-pi3k-and-mapk-inhibitors-overcomes-adaptive-kinome-resistance-to-single-agents-in-preclinical-models-of-glioblastoma
#17
Robert S McNeill, Demitra A Canoutas, Timothy J Stuhlmiller, Harshil D Dhruv, David M Irvin, Ryan E Bash, Steven P Angus, Laura E Herring, Jeremy M Simon, Kasey R Skinner, Juanita C Limas, Xin Chen, Ralf S Schmid, Marni B Siegel, Amanda E D Van Swearingen, Michael J Hadler, Erik P Sulman, Jann N Sarkaria, Carey K Anders, Lee M Graves, Michael E Berens, Gary L Johnson, C Ryan Miller
Background.: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) effectors of receptor tyrosine kinase (RTK) signaling represent promising candidates. Methods.: We previously developed a non-germline genetically engineered mouse model of GBM in which PI3K and MAPK are activated via Pten deletion and KrasG12D in immortalized astrocytes...
March 30, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28379339/synergyfinder-a-web-application-for-analyzing-drug-combination-dose-response-matrix-data
#18
Ianevski Aleksandr, Liye He, Tero Aittokallio, Jing Tang
Summary: Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner...
April 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28379332/synergyfinder-a-web-application-for-analyzing-drug-combination-dose-response-matrix-data
#19
Ianevski Aleksandr, Liye He, Tero Aittokallio, Jing Tang
Summary: Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner...
April 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28373177/glycemic-control-status-after-percutaneous-coronary-intervention-and-long-term-clinical-outcomes-in-patients-with-type-2-diabetes-mellitus
#20
Jin Kyung Hwang, Seung Hwa Lee, Young Bin Song, Joonghyun Ahn, Keumhee Carriere, Mi Ja Jang, Taek Kyu Park, Seung-Hyuk Choi, Jeong Hoon Yang, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon, Joo-Yong Hahn
BACKGROUND: Data on the association between glycemic control after percutaneous coronary intervention and clinical outcomes are limited and controversial in diabetic patients. METHODS AND RESULTS: We studied 980 patients with type 2 diabetes mellitus undergoing percutaneous coronary intervention using drug-eluting stents. Based on 2-year glycosylated hemoglobin A (HbA1c) levels, we divided patients into 2 groups of HbA1c<7.0 (n=489) and HbA1c≥7.0 (n=491). Propensity score-matched analysis was performed in 322 pairs...
April 2017: Circulation. Cardiovascular Interventions
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