IMP before and after treadmill running.

<p>IMP before and after treadmill running.</p

NIRS variables at rest, for cuff occlusion, and during and after treadmill running.

<p>NIRS variables at rest, for cuff occlusion, and during and after treadmill running.</p

Characterization of 28 CRPC bone metastases according to protein levels of the steroidogenic enzyme AKR1C3 (defined as high if the AKR1C3 immunostaining score was above median, >6, and low if the score was ≤6) and protein levels of LBD-truncated AR variants (AR-Vs; defined as high if the ratio between the truncated 80 kDa and the full length 110 kDa AR bands was ≥0.5, quartile 4, and low if the ratio was below 0.5, quartile 1–3).

<p>High levels AKR1C3 were basically found in metastases with low levels of AR-Vs and vice versa (P = 0.049, according to Chi-square test).</p

Simplified scheme of the key steps of testosterone and DHT steroidogenesis.

<p>Enzymes with significantly higher mRNA levels observed in bone metastases than in non-malignant and/or malignant prostate tissue are shown in bold and enzymes with significantly lower levels observed in bone metastases are shown in <i>italics</i>. Steroids secreted by the adrenal gland are highlighted in gray.</p

Immunohistochemical staining of AKR1C3 in bone metastases.

<p>A total score (ranging from 0–12) was obtained by multiplying the staining intensity score (0–3) in the tumor epithelial cells with the positive fraction score (1–4). (a) Histogram according to total AKR1C3 staining score in hormone-naïve (gray) and castration-resistant (black) bone metastases. (b) Representative section of bone metastasis with AKR1C3 total score 0. (c) Representative section of bone metastasis with AKR1C3 total score 12. Bar indicates 100 µM.</p

Clinical and histological characteristics of prostate cancer patients with bone metastases and treated with metastasis surgery.

<p>Continuous values are given as median (min-max values).</p>a<p>Castration-resistant patients had disease progression after long-term androgen deprivation therapy including surgical ablation, LHRH/GNRH agonist therapy, and therapy with anti-androgen (bicalutamide).</p>b<p>Radiation towards operation site.</p>c<p>The time between date of surgery and the latest follow-up examination or death.</p>d<p>Androgen receptor (AR) and prostate specific antigen (PSA) immunohistochemical staining scores were assessed according to details described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077407#s2" target="_blank">materials and methods</a> section.</p>e<p>Proliferation indexes were assessed as fractions of proliferating (Ki67 immunostained) tumor epithelial cell, according to details described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077407#s2" target="_blank">materials and methods</a> section.</p

Western blot analysis of 13 patient samples showing representative expression patterns of the full length AR (110 kDa) and of LDB-truncated AR variants (AR-Vs) of about 80 kDa in CRPC bone metastases.

<p>Analysis was performed using an antibody targeting the N-terminal domain of the AR. The 22Rv1 cell extract was included as a positive control.</p

Relative mRNA levels of key enzymes involved in steroid metabolism in non-malignant prostate tissue (n = 13), primary prostate tumor tissue (n = 13), and in hormone-naïve (HN, n = 9) and castration-resistant prostate cancer (CRPC, n = 45) bone metastases when quantified with real-time RT-PCR.

<p>All mRNA levels were corrected for mRNA levels of the housekeeping gene RPL13A and normalized to the median value of the primary tumor samples. *P<0.05. ** P<0.01, *** P<0.001. Open circles indicate outliers and extremes. X indicates extreme levels outside the scale.</p