Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters

BACKGROUND: Sarcoidosis is a multisystem disease of unknown origin characterized by the formation of noncaseating granulomas, in particular in the lungs, lymph nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used for large disfiguring lesions, generalized involvement, or recalcitrant lesions that did not respond to topical therapy. CASE PRESENTATIONS: We report three patients with recalcitrant cutaneous sarcoidosis who were treated with oral fumaric acid esters (FAE). Three female patients presented with cutaneous sarcoidosis that have proved to be refractory to various therapies, including corticosteroids and chloroquine. We treated the patients with FAE in tablet form using two formulations differing in strength (Fumaderm(® )initial, Fumaderm(®)). Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients. After treatment with FAE (4–12 months), a complete clearance of skin lesions was achieved in the three patients. The side effects observed in this trial correspond to the well-known spectrum of adverse effects of FAE (flush, minor gastrointestinal complaints, lymphopenia). CONCLUSIONS: On the basis of our findings FAE therapy seems to be a safe and effective regimen for patients with recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are necessary to confirm our preliminary results

The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance.

Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. Standard PCa therapeutic treatments include androgen-deprivation therapy and AR signaling inhibitors. Despite being successful in controlling the disease in the majority of men, the high frequency of disease progression to aggressive and therapy resistant stages (termed castrate resistant prostate cancer) has led to the search for new therapeutic targets. The p90 ribosomal S6 kinase (RSK1-4) family is a group of highly conserved Ser/Thr kinases that holds promise as a novel target. RSKs are effector kinases that lay downstream of the Ras/Raf/MEK/ERK signaling pathway, and aberrant activation or expression of RSKs has been reported in several malignancies, including PCa. Despite their structural similarities, RSK isoforms have been shown to perform nonredundant functions and target a wide range of substrates involved in regulation of transcription and translation. In this article we review the roles of the RSKs in proliferation and motility, cell cycle control and therapy resistance in PCa, highlighting the possible interplay between RSKs and AR in mediating disease progression. In addition, we summarize the current advances in RSK inhibitor development and discuss their potential clinical benefits

Using Discrete-time Analysis in the Performance Evaluation of Manufacturing Systems

Discrete-time analysis (DTA) is a modelling technique that is mainly applied to the analysis of communication systems. In this paper, we show how DTA can be adopted to the numerical analysis of manufacturing systems. The modelling concepts of DTA are introduced and the advantages of DTA over other methods like discrete-event simulation are indicated. We apply DTA to two sample applications, namely the analysis of a simple batch server and a batch server with bounded idle time

Using Discrete-time Analysis in the Performance Evaluation of Manufacturing Systems

Discrete--time analysis (DTA) is a modelling technique that is mainly applied to the analysis of communication systems. In this paper, we show how DTA can be adopted to the numerical analysis of manufacturing systems. The modelling concepts of DTA are introduced and the advantages of DTAover other methods like discrete--event simulation are indicated. We apply DTAtotwo sample applications, namely the analysis of a simple batch server and a batchserver with bounded idle time