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https://www.readbyqxmd.com/read/29732051/dual-targeting-biomimetic-delivery-for-anti-glioma-activity-via-remodeling-the-tumor-microenvironment-and-directing-macrophage-mediated-immunotherapy
#1
Pengfei Zhao, Yonghui Wang, Xuejia Kang, Aihua Wu, Weimin Yin, Yisi Tang, Jinyu Wang, Meng Zhang, Yifei Duan, Yongzhuo Huang
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity...
March 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29722447/trichloroethylene-exposure-results-in-the-phosphorylation-of-histone-h2ax-in-a-human-hepatic-cell-line-through-cytochrome-p450-2e1-mediated-oxidative-stress
#2
Tatsushi Toyooka, Yukie Yanagiba, Yuko Ibuki, Rui-Sheng Wang
Trichloroethylene (TCE), a chlorinated hydrocarbon, was recently reclassified as a human carcinogen by the International Agency for Research on Cancer. Genotoxic events are known to be crucial steps in the initiation of cancer. The genotoxic properties of TCE have been examined in many studies using a standard battery of genotoxicity tests both in vitro and in vivo. However, consistent results have not been obtained, and studies investigating the mechanism behind the genotoxicity of this compound are lacking...
May 3, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29721164/novel-therapeutic-features-of-disulfiram-against-hepatocellular-carcinoma-cells-with-inhibitory-effects-on-a-disintegrin-and-metalloproteinase-10
#3
Kaku Goto, Jun Arai, Anthony Stephanou, Naoya Kato
Our previous genome-wide association study identified the anti-tumor ligand MHC class I polypeptide-related sequence A ( MICA ) as a susceptibility gene for hepatitis C virus-induced hepatocellular carcinoma (HCC). We subsequently proved that pharmacological restoration of membrane-bound MICA in HCC cells boosted natural killer cell-mediated anti-cancer effects, confirming that a MICA sheddase, a disintegrin and metalloproteinase 10 (ADAM10), is a therapeutic target. We here searched for approved drugs with inhibitory effects on ADAM10 in vitro , and the anti-alcoholism agent, disulfiram, was identified...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720921/disulfiram-like-reaction-involving-ceftriaxone-in-a-pediatric-patient
#4
Stephen M Small, Rachel S Bacher, Sheridan A Jost
Several medications have been shown to cause disulfiram-like reactions in patients concomitantly exposed to ethanol, including specific cephalosporin antibiotics that possess a methylthiotetrazole substituent. Within the cephalosporin class, there are few reports of disulfiram-like reactions with ceftriaxone. This case report is the first to involve a pediatric patient, and it describes a mild but likely disulfiram-like reaction manifesting as facial flushing in an 8-year-old male upon receiving a ceftriaxone infusion preceded by a dose of prednisolone elixir (5% ethanol by volume) for presumed community-acquired pneumonia thought to be complicated by an asthma exacerbation...
March 2018: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29719204/drug-drug-interactions-in-the-treatment-for-alcohol-use-disorders-a-comprehensive-review
#5
REVIEW
Guerzoni Simona, Pellesi Lanfranco, Pini Luigi Alberto, Caputo Fabio
Drug interactions are one of the most common causes of side effects in polypharmacy. Alcoholics are a category of patients at high risk of pharmacological interactions, due to the presence of comorbidities, the concomitant intake of several medications and the pharmacokinetic and pharmacodynamic interferences of ethanol. However, the data available on this issue are limited. These reasons often frighten clinicians when prescribing appropriate pharmacological therapies for alcohol use disorder (AUD), where less than 15% of patients receive an appropriate treatment in the most severe forms...
April 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29715094/combined-gemcitabine-and-metronidazole-is-a-promising-therapeutic-strategy-for-cancer-stem-like-cholangiocarcinoma
#6
Makoto Kawamoto, Masayo Umebayashi, Hiroto Tanaka, Norihiro Koya, Sinichiro Nakagawa, Ken Kawabe, Hideya Onishi, Masafumi Nakamura, Takashi Morisaki
BACKGROUND/AIM: Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). MATERIALS AND METHODS: We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29693382/transition-metal-free-coupling-reaction-of-dithiocarbamates-with-indoles-c-s-bond-formation
#7
Azim Ziyaei Halimehjani, Sahar Shokrgozar, Petr Beier
A one-pot three-component route for the direct introduction of dithiocarbamates into indoles using a C-H sulfenylation strategy mediated by molecular iodine is disclosed. Various indole derivatives including 1-methylindole, 2-methylindole, 3-methylindole and 5-substituted indoles were applied successfully in this protocol to afford diverse indole-dithiocarbamates containing the dithiocarbamate group on the position two or three in good to high yields. The reactions do not require transition metals or disulfiram, use an environmentally benign solvent and simple commercially available starting materials...
April 25, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29665144/disulfiram-copper-targets-stem-cell-like-aldh-population-of-multiple-myeloma-by-inhibition-of-aldh1a1-and-hedgehog-pathway
#8
Na Jin, Xiaojian Zhu, Fanjun Cheng, Liling Zhang
Multiple myeloma stem cells (MMSCs) have been considered as the major cause resulting in relapse. Eradicating MMSCs may be an effective strategy to improve the outcome of multiple myeloma (MM). Increased activity of aldehyde dehydrogenase (ALDH) has been found in MMSCs, but whether inhibiting ALDH activity can eliminate MMSCs remains unknown. Disulfiram (DS) has been reported as an inhibitor of ALDH, and increasing studies showed it has anti-cancer effects in a copper (Cu)-dependent manner. In this study, we isolated ALDH+ cells of MM by Aldefluor assay and demonstrated they possessed tumorigenesis capacities in vitro and in vivo...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29615749/blocking-distinct-interactions-between-glioblastoma-cells-and-their-tissue-microenvironment-a-novel-multi-targeted-therapeutic-approach
#9
Melanie Mettang, Viola Meyer-Pannwitt, Georg Karpel-Massler, Shaoxia Zhou, Neil O Carragher, Karl Josef Föhr, Bernd Baumann, Lisa Nonnenmacher, Stefanie Enzenmüller, Meike Dahlhaus, Markus D Siegelin, Sebastien Stroh, Daniel Mertens, Pamela Fischer-Posovszky, E Marion Schneider, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
Due to the highly invasive nature of Glioblastoma (GB), complete surgical resection is not feasible, while motile tumour cells are often associated with several specific brain structures that enhance treatment-resistance. Here, we investigate the therapeutic potential of Disulfiram and Carbenoxolone, that inhibit two distinct interactions between GB and the brain tissue microenvironment: stress-induced cell-matrix adhesion and gap junction mediated cell-cell communication, respectively. Increase in cell numbers of tumour-initiating cells, which are cultured in suspension as cell clusters, and adherent differentiated cells can be blocked to a similar extent by Carbenoxolone, as both cell populations form gap junctions, but the adherent differentiated cells are much more sensitive to Disulfiram treatment, which - via modulation of NF-κB signalling - interferes with cell-substrate adhesion...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29571571/disulfiram-based-disulfides-as-narrow-spectrum-antibacterial-agents
#10
Jordan G Sheppard, Keely R Frazier, Pushkar Saralkar, Mohammad F Hossain, Werner J Geldenhuys, Timothy E Long
Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. In the final analysis, this investigation concluded that the S-octylthio derivative is a more effective growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more favorable cytotoxic and metabolic parameters over disulfiram...
March 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29570977/cystamine-and-disulfiram-inhibit-human-transglutaminase-2-via-an-oxidative-mechanism
#11
Brad Palanski, Chaitan Khosla
The catalytic activity of transglutaminase 2 (TG2), a ubiquitously expressed mammalian enzyme, is regulated by multiple post-translational mechanisms. Because elevated activity of TG2 in the extracellular matrix is associated with organ-specific diseases such as celiac disease and renal fibrosis, there is growing therapeutic interest in inhibitors of this enzyme. Cystamine, a symmetric disulfide compound, is one of the earliest reported TG2 inhibitors. Despite its widespread use as a tool compound to block TG2 activity in vitro and in vivo, its mechanism of action has remained unclear...
March 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29547841/suppressing-autophagy-enhances-disulfiram-copper-induced-apoptosis-in-non-small-cell-lung-cancer
#12
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29546352/confusion-in-sobriety-a-case-study-on-disulfiram-encephalopathy-in-a-middle-aged-male-patient
#13
Joyce Heung, Johannes Yin-Kwong Poon, Chi-Kwong Tung, Sze-Wing Yeung, Ming Lam
No abstract text is available yet for this article.
March 13, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/29519735/inhibition-of-histone-lysine-methyltransferases-g9a-and-glp-by-ejection-of-structural-zn-ii
#14
Danny C Lenstra, Abbas H K Al Temimi, Jasmin Mecinović
Histone lysine methyltransferases G9a and GLP are validated targets for the development of new epigenetic drugs. Most, if not all, inhibitors of G9a and GLP target the histone substrate binding site or/and the S-adenosylmethionine cosubstrate binding site. Here, we report an alternative approach for inhibiting the methyltransferase activity of G9a and GLP. For proper folding and enzymatic activity, G9a and GLP contain structural zinc fingers, one of them being adjacent to the S-adenosylmethionine binding site...
April 15, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29516013/update-of-aldh-as-a-potential-biomarker-and-therapeutic-target-for-aml
#15
REVIEW
Xiangchou Yang, Rongxin Yao, Hong Wang
Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ ALDHbr population or CD34+ CD38- ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29505711/mpeg-5k-b-plga-2k-pcl-3-4k-mct-mixed-micelles-as-carriers-of-disulfiram-for-improving-plasma-stability-and-antitumor-effect-in-vivo
#16
Linlin Miao, Jia Su, Xuezhi Zhuo, Lifeng Luo, Yihan Kong, Jingxin Gou, Tian Yin, Yu Zhang, Haibing He, Xing Tang
The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)- b-poly(lactide- co-glycolide)/poly(ε-caprolactone) (mPEG5k - b-PLGA2k /PCL3.4k ) micelles were developed for encapsulation of DSF by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed...
April 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29488114/a-smart-paclitaxel-disulfiram-nanococrystals-for-efficient-mdr-reversal-and-enhanced-apoptosis
#17
Imran Shair Mohammad, Wei He, Lifang Yin
PURPOSE: A multidrug resistance (MDR) modulator, disulfiram (DSF), was incorporated into pure paclitaxel (PTX) nanoparticles to construct a smart paclitaxel-disulfiram nanococrystals (PTX-DSF Ns) stabilized by β-lactoglobulin (β-LG), with the aim to reverse MDR and therefore enhnce cytotoxicity towards Taxol-resistant A549 cells (A549/TAX). METHOD: PTX-DSF Ns was prepared by antisolvent precipitation method. Flow cytometry was used to determine the cell uptake, drug efflux inhibition, cell cycle phase arrest and apoptosis...
February 27, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29462108/disulfiram-attenuates-morphine-or-methadone-withdrawal-syndrome-in-mice
#18
Anna de Cordé, Paweł Krząścik, Renata Wolińska, Patrycja Kleczkowska, Małgorzata Filip, Magdalena Bujalska-Zadrożny
Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioid abstinence syndrome, which occurs as a result of opioid withdrawal. Opioid dependence in mice was induced by subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg for 10 consecutive days...
February 16, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29444156/protein-s-glutathionylation-lowers-superoxide-hydrogen-peroxide-release-from-skeletal-muscle-mitochondria-through-modification-of-complex-i-and-inhibition-of-pyruvate-uptake
#19
Robert M Gill, Marisa O'Brien, Adrian Young, Danielle Gardiner, Ryan J Mailloux
Protein S-glutathionylation is a reversible redox modification that regulates mitochondrial metabolism and reactive oxygen species (ROS) production in liver and cardiac tissue. However, whether or not it controls ROS release from skeletal muscle mitochondria has not been explored. In the present study, we examined if chemically-induced protein S-glutathionylation could alter superoxide (O2●-)/hydrogen peroxide (H2O2) release from isolated muscle mitochondria. Disulfiram, a powerful chemical S-glutathionylation catalyst, was used to S-glutathionylate mitochondrial proteins and ascertain if it can alter ROS production...
2018: PloS One
https://www.readbyqxmd.com/read/29440564/fulminant-encephalopathy-with-unusual-brain-imaging-in-disulfiram-toxicity
#20
Dhanashree Peddawad, Shashank Nagendra, Rudrarpan Chatterjee, Hina Faldu, Akash Chheda
No abstract text is available yet for this article.
March 13, 2018: Neurology
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