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https://www.readbyqxmd.com/read/28107189/docosahexaenoic-acid-and-disulfiram-act-in-concert-to-kill-cancer-cells-a-mutual-enhancement-of-their-anticancer-actions
#1
Yang Jiao, Bethany N Hannafon, Roy R Zhang, Kar-Ming Fung, Wei-Qun Ding
We previously reported a synergistic anticancer action of clioquinol and docosahexaenoic acid (DHA) in human cancer cells. However, clioquinol has been banned from the clinic due to its neurotoxicity. This study identified disulfiram (DSF) as a substitute compound to clioquinol, acting in concert with DHA to more effectively kill cancer cells and suppress tumor growth. Treatment with DSF and DHA induced greater apoptotic cell death and suppression of tumor growth in vitro and in vivo, as compared to DSF and DHA used alone...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102089/disulfiram-moderately-restores-impaired-hepatic-redox-status-of-rats-subchronically-exposed-to-cadmium
#2
Aida Begic, Ana Djuric, Milica Ninkovic, Ivana Stevanovic, Dragan Djurdjevic, Milos Pavlovic, Katarina Jelic, Ana Pantelic, Goran Zebic, Bratislav Dejanovic, Ivan Stanojevic, Danilo Vojvodic, Petar Milosavljevic, Mirjana Djukic, Luciano Saso
Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2(·-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28093021/altering-ethanol-pharmacokinetics-to-treat-alcohol-use-disorder-can-you-teach-an-old-dog-new-tricks
#3
Carolina L Haass-Koffler, Fatemeh Akhlaghi, Robert M Swift, Lorenzo Leggio
Disulfiram was the first pharmacotherapy approved to treat alcohol use disorder in the 1950s. Disulfiram alters ethanol pharmacokinetics and causes uncomfortable reactions (e.g. headache, tachycardia, nausea, flushing and hypotension) when alcohol is consumed. Subsequently, a better understanding of the neurobiological pathways involved in alcohol use disorder led to the development of other medications (e.g. naltrexone and acamprosate). These neurobiological-based medications act on alcohol use disorder-related phenotypes including craving, stress, and/or withdrawal...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28064151/supervised-disulfiram-s-superior-effectiveness-in-alcoholism-treatment-ethical-methodological-and-psychological-aspects
#4
REVIEW
Colin Brewer, Emmanuel Streel, Marilyn Skinner
Disulfiram (DSF) causes the ALDH-mediated deterrence of alcohol consumption. We review recent meta-analyses showing the superior effectiveness of supervised disulfiram (SD) in alcoholism treatment compared with oral naltrexone or acamprosate (ACP). The success of SD is also consistent with the almost complete absence of alcoholism in Japanese homozygotes for 'inefficient' ALDH. However, SD is an underused treatment and some clinicians have ethical objections to DSF. We examine these objections and argue that they are based on a misunderstanding of how DSF works...
January 7, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28040834/aldehyde-dehydrogenase-activity-plays-no-functional-role-in-stem-cell-like-properties-in-anaplastic-thyroid-cancer-cell-lines
#5
Mika Shimamura, Tomomi Kurashige, Norisato Mitsutake, Yuji Nagayama
Recent studies have revealed that aldehyde dehydrogenase (ALDH) is a candidate marker for thyroid cancer stem cells, although its activity is flexible. The goal of this study is to clarify the functional significance of ALDH enzymatic activity on thyroid cancer stem cells properties in anaplastic thyroid cancer cell lines. In vitro sphere formation assay was used to judge the stemness of 4 anaplastic thyroid cancer cell lines (FRO, ACT1, 8505C, and KTC3). Two well-known ALDH inhibitors, N,N-diethylaminobenzaldehyde (DEAB) and disulfiram (DS), were first used...
December 31, 2016: Endocrine
https://www.readbyqxmd.com/read/28017615/pharmacological-activation-of-aldehyde-dehydrogenase-2-promotes-osteoblast-differentiation-via-bone-morphogenetic-protein-2-and-induces-bone-anabolic-effect
#6
Monika Mittal, Subhashis Pal, Shyamsundar Pal China, Konica Porwal, Kapil Dev, Richa Shrivastava, Kanumuri Siva Rama Raju, Mamunur Rashid, Arun Kumar Trivedi, Sabyasachi Sanyal, Muhammad Wahajuddin, Smrati Bhaduria, Rakesh Maurya, Naibedya Chattopadhyay
Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2)...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27984008/treatment-of-alcohol-use-disorder-in-patients-with-alcoholic-liver-disease
#7
REVIEW
Lorenzo Leggio, Mary R Lee
Alcohol is a leading cause of liver disease worldwide. Although alcohol abstinence is the crucial therapeutic goal for patients with alcoholic liver disease, these patients have less access to psychosocial, behavioral and/or pharmacological treatments for alcohol use disorder. Psychosocial and behavioral therapies include 12-step facilitation, brief interventions, cognitive behavioral therapy, and motivational enhancement therapy. In addition to medications approved by the Food and Drug Administration (FDA) for alcohol use disorder (disulfiram, naltrexone and acamprosate), recent efforts to identify potential new treatments have yielded promising candidate pharmacotherapies...
October 28, 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27973926/drug-induced-liver-injury-a-cohort-study-on-patients-referred-to-the-danish-transplant-center-over-a-five-year-period
#8
Mille Baekdal, Henriette Ytting, Mette Skalshøi Kjær
OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors of poor outcome. MATERIALS AND METHODS: We identified all patients diagnosed with DILI at the Department of Hepatology, Rigshospitalet, from March 2007 to November 2012...
December 15, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27915005/development-and-characterisation-of-disulfiram-loaded-plga-nanoparticles-for-the-treatment-of-non-small-cell-lung-cancer
#9
Mohammad Najlah, Zahima Ahmed, Mohammed Iqbal, Zhipeng Wang, Patrica Tawari, Weiguang Wang, Christopher McConville
Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4min) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27898047/inhibition-of-urease-by-disulfiram-an-fda-approved-thiol-reagent-used-in-humans
#10
Ángel Gabriel Díaz-Sánchez, Emilio Alvarez-Parrilla, Alejandro Martínez-Martínez, Luis Aguirre-Reyes, Jesica Aline Orozpe-Olvera, Miguel Armando Ramos-Soto, José Alberto Núñez-Gastélum, Bonifacio Alvarado-Tenorio, Laura Alejandra de la Rosa
Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors...
November 26, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27895076/mesothelial-cells-create-a-novel-tissue-niche-that-facilitates-gastric-cancer-invasion
#11
Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells...
November 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#12
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27882330/aldh2-inhibition-potentiates-high-glucose-stress-induced-injury-in-cultured-cardiomyocytes
#13
Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Suresh Selvaraj Palaniyandi
Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27846399/sensory-motor-axonal-polyneuropathy-involving-cranial-nerves-an-uncommon-manifestation-of-disulfiram-toxicity
#14
Telma Santos, António Martins Campos, Hugo Morais
Disulfiram (tetraethylthiuram disulfide) has been used for the treatment of alcohol dependence. An axonal sensory-motor polyneuropathy with involvement of cranial pairs due to disulfiram is exceedingly rare. The authors report a unique case of an extremely severe axonal polyneuropathy involving cranial nerves that developed within weeks after a regular dosage of 500mg/day disulfiram. To the authors best knowledge, such a severe and rapidly-progressive course has never been described with disulfiram dosages of only 500mg/day...
January 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/27831632/disulfiram-as-a-candidate-nf-%C3%AE%C2%BAb-and-proteasome-inhibitor-prevents-endometriotic-implant-growing-in-a-rat-model-of-endometriosis
#15
O Celik, A Ersahin, M Acet, N Celik, Y Baykus, R Deniz, E Ozerol, I Ozerol
OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27803460/an-ophthalmic-formulation-of-disulfiram-nanoparticles-prolongs-drug-residence-time-in-lens
#16
Noriaki Nagai, Yu Mano, Yoshimasa Ito
Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27793743/dopamine-beta-hydroxylase-participate-in-the-immunoendocrine-responses-of-hypothermal-stressed-white-shrimp-litopenaeus-vannamei
#17
Winton Cheng, Ya-Wen Ka, Chin-Chyuan Chang
Dopamine beta-hydroxylase (DBH) plays a critical role in catecholamine (CA) synthesis of neuroendocrine regulatory network, and is suggested to be involved in the immunoendocrine responses of invertebrate against bacterial challenge. DBH has been identified in white shrimp, Litopenaeus vannamei, and further investigation on its potential function was conducted after hypothermal stress, pharmaceutical inhibition and gene silencing in the present study. Cloned DBH L. vannamei (LvDBH), belonging to the Copper type II, ascorbate-dependent monooxygenases, was characterized by a DOMON domain, a Cu2_monooxygen domain and three glycosylation sites, and its expression was abundant in thoracic ganglia and haemocytes determined by quantitative real-time PCR...
December 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27754304/lbos-02-05-inhibitors-of-dopamine-%C3%AE-hydroxylase-obtained-by-structure-based-methods-exhibited-anti-hypertensive-effect-in-l-name-induced-hypertensive-rats
#18
Sanjay Kumar Dey, Pankaj Prabhakar, Manisha Saini, Toyanji Joseph, B K Thelma, Subir K Maulik, Suman Kundu
OBJECTIVE: To identify novel inhibitors of dopamine beta hydroxylase (DBH) and evaluate their antihypertensive properties in L-NAME induced hypertensive rat model. DESIGN AND METHOD: An experimentally validated computational model for hDBH, built in our lab, was used for structure-based, rational drug-design. The three-dimensional model was used for virtual-screening against small molecule databases from NCI, USA and elsewhere. Identified top hits were then tested in vitro against DBH with known inhibitors nepicastat and disulfiram as controls...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27725388/design-of-novel-ophthalmic-formulation-containing-drug-nanoparticles-and-its-usefulness-as-anti-glaucoma-drugs
#19
Noriaki Nagai
 The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27708770/the-cytotoxic-mechanisms-of-disulfiram-and-copper-ii-in-cancer-cells
#20
Patricia Erebi Tawari, Zhipeng Wang, Mohammad Najlah, Chi Wai Tsang, Vinodh Kannappan, Peng Liu, Christopher McConville, Bin He, Angel L Armesilla, Weiguang Wang
The anticancer activity of disulfiram (DS) is copper(ii) (Cu)-dependent. This study investigated the anticancer mechanisms of DS/Cu using in vitro cytotoxicity and metabolic kinetic analysis. Our study indicates that DS/Cu targets cancer cells by the combination of two types of actions: (1) instant killing executed by DS/Cu reaction generated reactive oxygen species; (2) delayed cytotoxicity introduced by the end product, DDC-Cu. Nanoencapsulation of DS might shed light on repositioning of DS into cancer treatment...
November 19, 2015: Toxicology Research
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