The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens.

Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.

No abstract

SUMMARY We report a patient with severe Crohn's disease and the short bowel syndrome on parenteral feeding who was not responding to conventional therapy and underwent treatment with cyclosporin (CyA) given initially intravenously and subsequently orally in each of two courses. Plasma drug concentrations were largely kept within the therapeutic range but wide variability was observed on oral therapy. Improvement both clinically and by objective assessment, was observed on intravenous CyA therapy, but was not sustained when the drug was given orally for several months. None of the side effects observed resisted treatment or was severe enough to warrant discontinuation of therapy. These findings suggest that there may be a place for intravenous CyA therapy in patients with severe Crohn's disease who do not respond to conventional therapy or to oral treatment with CyA.

Cocaine (2 × 10−6m and 10−5m) produced 2 and 7 fold shifts to the left of the dose‐response curve to (—)‐noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. Desmethylimipramine (DMI, 10 −7 to 10−6m) produced no significant potentiation of the response of cat spleen strips to (—)‐noradrenaline. At 10−5 M DMI decreased the maximum response. Cocaine (10−5m) produced a 3.3 fold shift to the left of the dose‐response curve whereas DMI (10−6m) had no effect on the dose‐response curve to oxymetazoline in cat splenic capsular strips. Cocaine (10−5m) in the presence of phentolamine (10−6m) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. Cocaine (10−5m) had no effect on the dose‐response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. The potentiating effect of cocaine (10−5m) on responses of spleen strips to (—)‐noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 × 10−5m). It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.