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https://www.readbyqxmd.com/read/29148232/disulfiram-combined-with-copper-inhibits-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma-through-the-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-pathways
#1
Yi Li, Li-Hui Wang, Hao-Tian Zhang, Ya-Ting Wang, Shuai Liu, Wen-Long Zhou, Xiang-Zhong Yuan, Tian-Yang Li, Chun-Fu Wu, Jing-Yu Yang
Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29135106/evidence-for-the-efficacy-of-disulfiram-and-copper-combination-in-glioblastoma-multiforme-a-propos-of-a-case
#2
Petros N Karamanakos, Dimitrios T Trafalis, Dionysios J Papachristou, Eleftheria S Panteli, Maria Papavasilopoulou, Andreas Karatzas, Dimitrios Kardamakis, Georgios Nasioulas, Marios Marselos
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29128392/adrenergic-manipulation-inhibits-pavlovian-conditioned-approach-behaviors
#3
Kyle Z Pasquariello, Marina Han, Cagla Unal, Paul J Meyer
Environmental rewards and Pavlovian reward cues can acquire incentive salience, thereby eliciting incentive motivational states and instigate reward-seeking. In rats, the incentive salience of food cues can be measured during a Pavlovian conditioned approach paradigm, in which rats engage in cue-directed approach ("sign-tracking") or approach the food delivery location ("goal-tracking"). While it has been shown that dopamine signaling is necessary for sign-tracking, some studies have suggested that norepinephrine is involved in learning to sign-track as well...
November 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29120249/alcohol-addiction-the-safety-of-available-approved-treatment-options
#4
Mariangela Antonelli, Anna Ferrulli, Luisa Sestito, Gabriele A Vassallo, Claudia Tarli, Carolina Mosoni, Maria M Rando, Antonio Mirijello, Antonio Gasbarrini, Giovanni Addolorato
Alcohol Use Disorder (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a "temporary recommendation for use" in France. Areas covered. The safety of the medications mentioned above on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed...
November 9, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29069808/targeting-the-cancer-stem-cell-marker-aldehyde-dehydrogenase-1-to-circumvent-cisplatin-resistance-in-nsclc
#5
Lauren MacDonagh, Michael F Gallagher, Brendan Ffrench, Claudia Gasch, Eamon Breen, Steven G Gray, Siobhan Nicholson, Niamh Leonard, Ronan Ryan, Vincent Young, John J O'Leary, Sinead Cuffe, Stephen P Finn, Kenneth J O'Byrne, Martin P Barr
Non-small cell lung cancer (NSCLC) accounts for a large proportion of cancer deaths and is characterized by low treatment response rates and poor overall prognosis. In the absence of specific treatable mutations, cisplatin-based chemotherapy plays an important role in the treatment of this disease. Unfortunately, the development of resistance has become a major therapeutic challenge in the use of this cytotoxic drug. Elucidating the mechanisms underlying this resistance phenotype, may result in the development of novel agents that enhance sensitivity to cisplatin in lung cancer patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#6
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29029481/cell-cycle-specific-radiosensitisation-by-the-disulfiram-and-copper-complex
#7
Mathias Tesson, Giorgio Anselmi, Caitlin Bell, Robert Mairs
The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016275/effectiveness-of-psychoanalytic-interactional-group-therapy-vs-behavioral-group-therapy-in-routine-outpatient-treatment-of-alcohol-dependent-patients
#8
Peter W Nyhuis, Eva Niederhofer, Norbert Scherbaum, Fabrizio Schifano, Udo Bonnet, Nikolai Dembski, Anna Niederhofer, Michael Specka, Meike Tenbergen
BACKGROUND: The cognitive behavioral therapy has been extensively investigated to assess relapse prevention rates in patients with alcohol dependence. In contrast, only little is known regarding the effectiveness of psychoanalytical psychotherapy in relapse prevention, although this treatment is widely used and especially so in Germany. The aim of this quasi-randomized study was to compare the effectiveness of these two group treatments' approaches under the condition of routine outpatient treatment in a non-university hospital...
October 10, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28974447/synergistic-toxicity-of-epigallocatechin-3-gallate-and-diethyldithiocarbamate-a-lethal-encounter-involving-redox-active-copper
#9
Ke Zhang, Ruixia Dong, Kang Sun, Xiaoxiao Wang, Jiajia Wang, Chung S Yang, Jinsong Zhang
Dithiocarbamates (DTC) are widely used in agricultural, industrial and therapeutic domains. There are ample opportunities for human exposure to DTC. Green tea extracts, with epigallocatechin-3-gallate (EGCG) being the most abundant constituent, have been used as dietary supplements for body weight reduction. Our hypothesis is that DTC can act as a copper ionophore to increase hepatic levels of redox-active copper which promotes EGCG auto-oxidation to produce oxidative stress and toxicity. The results of the present study in a mouse model is consistent with this hypothesis, showing that co-administration of EGCG and diethyldithiocarbamate - a metabolite of disulfiram (a drug for alcohol aversion therapy), both at tolerable levels, caused lethality...
September 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28959434/naltrexone-efficacy-in-treating-alcohol-use-disorder-in-individuals-with-comorbid-psychosis-a-systematic-review
#10
REVIEW
Martyna Sawicka, Derek K Tracy
BACKGROUND: Psychotic illnesses, such as schizophrenia, are typically enduring and disabling conditions, impacting individual, family, and societal outcomes. Individuals with these face greater vulnerabilities in developing alcohol-use disorder (AUD). Furthermore, the nature of psychoses, often manifesting with paranoia, cognitive impairment, a lack of insight, sub-optimal treatment adherence, and stigma from others, means that they can pose unique treatment challenges when these two conditions comorbidly occur...
September 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28956927/quantitative-and-systems-pharmacology-1-in-silico-prediction-of-drug-target-interactions-of-natural-products-enables-new-targeted-cancer-therapy
#11
Jiansong Fang, Zengrui Wu, Chuipu Cai, Qi Wang, Yun Tang, Feixiong Cheng
Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach...
October 13, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28950195/octa-arginine-modified-lipid-emulsions-as-a-potential-ocular-delivery-system-for-disulfiram-a-study-of-the-corneal-permeation-transcorneal-mechanism-and-anti-cataract-effect
#12
Chang Liu, Qi Lan, Wei He, Changlu Nie, Chunjuan Zhang, Tonghua Xu, Tongying Jiang, Siling Wang
The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8...
August 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28919445/cognitive-effects-of-labeled-addictolytic-medications
#13
REVIEW
Camille Noélie Pujol, Cecilia Paasche, Vincent Laprevote, Benoit Trojak, Pierre Vidailhet, Elisabeth Bacon, Laurence Lalanne
INTRODUCTION: Alcohol, tobacco, and illegal drug usage is pervasive throughout the world, and abuse of these substances is a major contributor to the global disease burden. Many pharmacotherapies have been developed over the last 50years to target addictive disorders. While the efficacy of these pharmacotherapies is largely recognized, their cognitive impact is less known. However, all substance abuse disorders are known to promote cognitive disorders like executive dysfunction and memory impairment...
September 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28918668/current-status-and-future-prospects-for-the-development-of-substance-abuse-vaccines
#14
R David Heekin, Daryl Shorter, Thomas R Kosten
Substance use disorders (SUD) are a significant threat to both individual and public health. To date, SUD pharmacotherapy has focused primarily on agonist medications (i.e. nicotine replacement therapy for tobacco use disorder; methadone and buprenorphine for opioid use disorder), antagonist medications (i.e. naltrexone for opioid use disorder), and aversive therapy (i.e. disulfiram for alcohol use disorder). Pharmacotherapeutic approaches utilizing an immunological framework for medication development represent an important focus of study for treatment of these illnesses...
November 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28887129/disulfiram-is-a-slow-binding-partial-noncompetitive-inhibitor-of-20s-proteasome-activity
#15
Brian B Hasinoff, Daywin Patel
The alcohol abuse drug disulfiram has also been shown to exhibit potent cell growth inhibitory and anticancer activity. While a number of cellular and animal studies have suggested that disulfiram exhibits its anticancer activity through interaction with the proteasome, direct evidence for inhibition of proteasome activity is lacking. In this study we show that disulfiram potently inhibits the chymotrypsin-like activity of purified human 20S proteasome at low micromolar pharmacological concentrations. The enzyme progress curves displayed characteristics of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib...
November 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28875004/a-comparative-cytotoxic-evaluation-of-disulfiram-encapsulated-plga-nanoparticles-on-mcf-7-cells
#16
Hamidreza Fasehee, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Seyed-Hamidollah Ghaffari, Shahab Faghihi
Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials andMethods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28864067/a-novel-chemoradiation-targeting-stem-and-nonstem-pancreatic-cancer-cells-by-repurposing-disulfiram
#17
Juan Cong, Yangyang Wang, Xiao Zhang, Nan Zhang, Ling Liu, Klara Soukup, Theodoros Michelakos, Theodore Hong, Albert DeLeo, Lei Cai, Francesco Sabbatino, Soldano Ferrone, Hang Lee, Vera Levina, Bryan Fuchs, Kenneth Tanabe, Keith Lillemoe, Cristina Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of 8% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28827047/high-drinking-in-the-dark-hdid-mice-are-sensitive-to-the-effects-of-some-clinically-relevant-drugs-to-reduce-binge-like-drinking
#18
John C Crabbe, Angela R Ozburn, Pamela Metten, Amanda Barkley-Levenson, Jason P Schlumbohm, Stephanie E Spence, Wyatt R Hack, Lawrence C Huang
BACKGROUND: There is a serious public health need for better understanding of alcohol use disorder disease mechanisms and for improved treatments. At this writing, only three drugs are approved by the Food and Drug Administration as medications to treat alcohol use disorders - disulfiram, naltrexone, and acamprosate. Binge drinking is a form of abusive alcohol drinking defined by the NIAAA as a drinking to blood alcohol levels (BALs)>0.08% during a period of approximately 2h. To model genetic risk for binge-like drinking, we have used selective breeding to create a unique animal model, High Drinking in the Dark (HDID) mice...
September 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28811616/synthesis-free-pet-imaging-of-brown-adipose-tissue-and-tspo-via-combination-of-disulfiram-and-64-cucl2
#19
Jing Yang, Jian Yang, Lu Wang, Anna Moore, Steven H Liang, Chongzhao Ran
PET imaging is a widely applicable but a very expensive technology. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18 kDa (TSPO) via a combination of disulfiram, an FDA approved drug for alcoholism, and (64)CuCl2 (termed (64)Cu-Dis). In this method, a step-wise injection protocol of (64)CuCl2 and disulfiram was used to accomplish the purpose of synthesis-free...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768860/zinc-finger-containing-cellular-transcription-corepressor-zbtb25-promotes-influenza-virus-rna-transcription-and-is-a-target-for-zinc-ejector-drugs
#20
Shu-Chuan Chen, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNA interference (RNAi) genomic library screen. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it...
October 15, 2017: Journal of Virology
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