- Disulfiram inhibits epithelial-mesenchymal transition through TGFβ-ERK-Snail pathway independently of Smad4 to decrease oral squamous cell carcinoma metastasis [Corrigendum]. [Journal Article]
- CMCancer Manag Res 2019; 11:4617
- Interventions for cisplatin-induced hearing loss in children and adolescents with cancer. [Review]
- LCLancet Child Adolesc Health 2019 May 31
- The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acqui…
The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acquisition development. Previous randomised trials assessed systemic drugs such as amifostine, sodium diethyldithiocarbamate or disulfiram, and sodium thiosulfate. Amifostine, sodium diethyldithiocarbamate, and disulfiram did not show hearing preservation. Paediatric trials assessing sodium thiosulfate showed efficacy in terms of hearing protection. The SIOPEL 6 trial consisted solely of patients with localised hepatoblastoma and no effects on survival were shown. In the ACCL0431 trial, which included heterogeneous patients, a post-hoc analysis showed significantly worse overall survival among patients who had disseminated disease receiving sodium thiosulfate than among controls, but not among those with localised disease. Intratympanically administered drugs have mainly been assessed in adults and include N-acetylcysteine and dexamethasone. Inconsistent effects of these drugs were identified but these studies were limited by design, small sample size, and statistical approach. Future studies of systemic drugs will need to consider the measurement of disease outcomes through study design and sample size, and ototoxicity endpoints should be harmonised to enhance comparability between trials.
- Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases. [Journal Article]
- AAntibiotics (Basel) 2019 May 30; 8(2)
- Three patients, each of whom had required intensive open-ended antimicrobial therapy for control of the symptoms of chronic relapsing neurological Lyme disease and relapsing babesiosis, were able to …
Three patients, each of whom had required intensive open-ended antimicrobial therapy for control of the symptoms of chronic relapsing neurological Lyme disease and relapsing babesiosis, were able to discontinue treatment and remain clinically well for periods of observation of 6-23 months following the completion of a finite course of treatment solely with disulfiram. One patient relapsed at six months and is being re-treated with disulfiram.
- The repurposed drug, disulfiram, inhibits urease and aldehyde dehydrogenase and prevents in vitro growth of the oomycete Pythium insidiosum. [Journal Article]
- AAAntimicrob Agents Chemother 2019 May 28
- Pythium insidiosum is an oomycete microorganism that causes a life-threatening infectious disease, called pythiosis, in humans and animals. The disease has been increasingly reported worldwide. Conve…
Pythium insidiosum is an oomycete microorganism that causes a life-threatening infectious disease, called pythiosis, in humans and animals. The disease has been increasingly reported worldwide. Conventional antifungal drugs are ineffective against P. insidiosum As to treat pythiosis, it requires extensive removal of infected tissue (i.e., eye, leg), but inadequate surgery and recurrent infection often occur. A more effective treatment is needed for pythiosis patients. Drug repurposing is a promising strategy for the identification of an FDA-approved drug for the control of P. insidiosum Disulfiram has been approved to treat alcoholism, but it exhibits antimicrobial activity against various pathogens. In this study, we explored whether disulfiram possesses an anti-P. insidiosum activity. All 27 P. insidiosum strains, isolated from various hosts and geographic areas, were susceptible to disulfiram, in a dose-dependent manner. MIC range of disulfiram against P. insidiosum (8 - 32 mg/L) was in line with that of other pathogens. Proteogenomic analysis indicated that several potential targets of disulfiram (i.e., aldehyde dehydrogenase and urease) were present in P. insidiosum By homology modeling and molecular docking, disulfiram can bind the putative aldehyde dehydrogenase and urease of P. insidiosum at low energies (i.e., -6.1 and -4.0 Kcal/mol, respectively). Disulfiram diminished the biochemical activities of these enzymes. In conclusion, disulfiram can inhibit the growth of many pathogenic microorganisms, including P. insidiosum The drug can bind and inactivate multiple proteins of P. insidiosum, which may contribute to its broad antimicrobial property. Drug repurposing of disulfiram could be a new treatment option for pythiosis.
- Disulfiram inhibits epithelial-mesenchymal transition through TGFβ-ERK-Snail pathway independently of Smad4 to decrease oral squamous cell carcinoma metastasis. [Journal Article]
- CMCancer Manag Res 2019; 11:3887-3898
- CONCLUSIONS: These results indicated that Dsf inhibited EMT of OSCC in vitro and in vivo independently of Smad4 through suppression of the TGFβ-ERK-Snail pathway, suggesting the broad-spectrum anticancer potential of Dsf for clinical use against OSCC.
- Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer. [Journal Article]
- BBiomacromolecules 2019 Jun 10; 20(6):2372-2383
- Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC)2, is the cruc…
Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC)2, is the crucial DSF's metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu(II) and carboxylic groups in poly(ethylene glycol)- b-poly(ester-carbonate) (PEC) for efficient loading of Cu(DDC)2, which was generated by the in situ reaction of DSF and Cu(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu(II), and PEC. These Cu(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu(DDC)2-based chemotherapy and chemodynamic therapy mediated by bioavailable Cu(II) that was not in the form of Cu(DDC)2. The in vivo antitumor results demonstrated that the Cu(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.
- An integrative bioinformatics pipeline to demonstrate the alteration of the interaction between the ALDH2*2 allele with NAD+ and Disulfiram. [Journal Article]
- JCJ Cell Biochem 2019 May 19
- Alcohol use disorder (AUD) is a multifactorial psychiatric behavior disorder. Disulfiram is the first approved drug by the Food and Drug Administration for alcohol-dependent patients, which targets t…
Alcohol use disorder (AUD) is a multifactorial psychiatric behavior disorder. Disulfiram is the first approved drug by the Food and Drug Administration for alcohol-dependent patients, which targets the ALDH2 enzyme. Several genes are known to be involved in alcohol metabolism; mutations in any of these genes are known to be associated with AUD. The E504K mutation in the ALDH2 of the precursor protein or the E487K of the mature protein (E504K/E487K; ALDH2*2 allele) is carried by approximately 8% of the world population. In this study, we aimed to test the known inactive allele ALDH2*2, to validate the use of our extensive computational pipeline (in silico tools, molecular modeling, and molecular docking) for testing the interaction between the ALDH2*2 allele, NAD+, and Disulfiram. In silico predictions showed that the E504K variant of ALDH2 to be pathogenic and destabilizing with the maximum number of prediction in silico tools. Consequently, we studied the effect of this mutation mainly on the interaction between NAD+ -E504K and Disulfiram-E504K complexes using molecular docking technique, and molecular dynamics (MD) analysis. From the molecular docking analysis with NAD+ , we observed that the interaction affinity of the NAD+ decreases with the impact of E504K variant. On the other hand, the drug Disulfiram showed similar interaction in both the native and mutant ALDH2 proteins. Further, the comprehensive MD analysis predicted that the E504K destabilizes the protein and influences the NAD+ and Disulfiram interactions. Our findings reveal that the interaction of NAD+ to the protein is disturbed by the E504K/E487K variant whereas the drug Disulfiram has a similar effect as both native ALDH2 and ALDH2 bearing E504K/E487K variant. This study provides a platform to understand the effect of E504K/E487K on the molecular interaction with NAD+ and Disulfiram.
- Dispensing of medication for alcohol use disorder; an examination of large databases in a New Zealand context. [Journal Article]
- NZN Z Med J 2019 May 17; 132(1495):48-53
- CONCLUSIONS: Overall rates of dispensing were relatively low. Antidepressants followed by quetiapine were the most common treatments. In contrast, disulfiram and naltrexone were only used for a minority of clients. This suggests inadequate and poorly targeted pharmacological treatments are used for the treatment of alcohol use disorders in New Zealand.
- Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction. [Journal Article]
- AJAm J Addict 2019 May 14
- CONCLUSIONS: We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels. (Am J Addict 2019:1-7).
New Search Next
- Drug repurposing to overcome resistance to various therapies for colorectal cancer. [Review]
- CMCell Mol Life Sci 2019 May 13
- Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance rema…
Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance remains a huge challenge in clinics, leading to invariable occurrence of disease progression after treatment initiation. While novel drug development is unfavorable in terms of time frame and costs, drug repurposing is one of the promising strategies to combat resistance. This approach refers to the application of clinically available drugs to treat a different disease. With the well-established safety profile and optimal dosing of these approved drugs, their combination with current cancer therapy is suggested to provide an economical, safe and efficacious approach to overcome drug resistance and prolong patient survival. Here, we review both preclinical and clinical efficacy, as well as cellular mechanisms, of some extensively studied repurposed drugs, including non-steroidal anti-inflammatory drugs, statins, metformin, chloroquine, disulfiram, niclosamide, zoledronic acid and angiotensin receptor blockers. The three major treatment modalities in the management of colorectal cancer, namely classical cytotoxic chemotherapy, molecular targeted therapy and immunotherapy, are covered in this review.