Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan

<p>Abstract</p> <p>Background</p> <p>This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients.</p> <p>Methods</p> <p>A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes.</p> <p>Results</p> <p>Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01).</p> <p>Conclusion</p> <p>Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01447550">NCT01447550</a></p

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics