Track topics on Twitter Track topics that are important to you
The primary hypothesis of this study is that disulfiram is a DNA methyltransferase inhibitor and may provide benefit for patients with prostate cancer by restoration of tumor suppressor genes. Disulfiram is a potent DNA methyltransferase 1 (DNMT1) inhibitor in vitro in our laboratory and it was recently found as one of the most potent inhibitors for PCa growth in vitro by screening the Johns Hopkins Drug Library. Based on this data, extensive in vitro and in vivo studies have been performed to explore its potential antitumor activities in prostate PCa. Using both androgen sensitive and insensitive PCa cell lines, we have confirmed that disulfiram can demethylate known highly methylated tumor suppressor genes such as APC and RARß in PCa cell lines. Disulfiram inhibited PCa cell growth in vitro and in vivo. In addition to these new findings, the antitumor activity of disulfiram and its other possible mechanisms of action are well documented in literature. Disulfiram has been shown to induce apoptosis in a number of cell lines including PCa. A variety of underlying mechanisms of anticancer activity have been reported. Disulfiram has been shown to reduce angiogenesis, inhibit DNA topoisomerases, inhibit nuclear factor κB, induce p21 and p53 with G1/S cell cycle arrest, induce pro-apoptotic redox-related mitochondrial membrane permeabilization, inactivate Cu/Zn superoxide dismutase by Cu2+ complexation, inhibit Zn2+-dependent matrix metalloproteinases, and prevent tumor invasion or metastasis. The disulfiram analogue pyrrolidine dithiocarbamate (PDTC) has been shown to inhibit proteasomal activity in combination with copper in human breast and PCa cell lines. Also, disulfiram or its metabolites permanently inactivate the human multidrug resistance P-glycoprotein or reverses either MDR1- or MRP1-mediated drug efflux.
Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Johns Hopkins Hospital
Johns Hopkins University
Published on BioPortfolio: 2014-08-27T03:13:53-0400
The purpose of this study is to determine the safety and optimal dosing of intravenous copper chloride and disulfiram in men with metastatic castrate-resistant prostate cancer (CRPC). Elig...
The purpose of this study is to determine whether disulfiram might be a safe and effective treatment for cocaine and/or alcohol dependence in patients with HIV disease. This research is de...
Disulfiram (Antabuse®) is a well-tolerated, cheap, generic drug that has been in use since the 1950s to treat alcoholism. There is now an increasing amount of independent preclinical data...
Recent studies in laboratory animals demonstrate the ability of disulfiram to significantly inhibit the growth and metastasis of a mouse model of lung cancer. Work with cells in vitro s...
The problem of cocaine dependence remains a major medical, social, and legal concern. Several studies have suggested that disulfiram may be beneficial for the treatment of cocaine dependen...
The avidity of prostate cancer cells for copper sensitizes them to cytotoxicity by disulfiram, a dithiocarbamate-containing drug approved for alcohol aversion therapy. While disulfiram has received at...
Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate e...
To examine whether age-related reference ranges for "normal" prostate-specific antigen (PSA) change (determined in men without prostate cancer) can be used to identify men at high risk of having prost...
Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anti-cancer effects in various malignant tumors. In this study, we investigated the anti-cancer effects and mecha...
The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controver...
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).
Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.
A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...