Citations

Abstract Aberrant activation of the androgen receptor (AR) by the ErbB2/ErbB3 heterodimer contributes to the development of hormone resistance in prostate cancer. EBP1, an ErbB3-binding protein, acts as an AR corepressor. As EBP1 is decreased in preclinical models of hormone-refractory prostate cancer, we studied the expression of EBP1 in human prostate cancer. We found that the expression of the EBP1 gene was significantly decreased in prostate cancer tissues compared with benign prostate at both mRNA and protein levels. Restoration of EBP1 expression in the hormone-refractory LNCaP C81 cell line led to an amelioration of the androgen-independent phenotype based on established biological criteria and a reduction in the expression of a cohort of AR target genes. The ability of the ErbB3 ligand heregulin (HRG) to stimulate growth and AKT phosphorylation of hormone-refractory prostate cancer cells was abolished. Abrogation of EBP1 expression by short hairpin RNA in hormone-dependent LNCaP cells, which undergo apoptosis in response to HRG, resulted in HRG-stimulated cell growth. Restoration of EBP1 expression decreased the tumorigenicity of C81 xenografts in female mice, whereas elimination of EBP1 expression enhanced the ability of LNCaP cells to grow in female mice. Our data support a role for EBP1 in the development of hormone-refractory prostate cancer via inhibition of both AR- and HRG-stimulated growth and present a novel strategy for treating androgen-refractory prostate cancer. [Mol Cancer Ther 2008;7(10):3176–86]

Sacral neuromodulation is a therapeutic option for women with detrusor overactivity and more recently has been used in patients with fecal incontinence and slow-transit constipation. A 47-year-old woman presented with chronic constipation since childhood. She used multiple laxatives, fiber supplements, and enemas, all without success, and defecated only once per week. Extensive investigations, including barium enema, colonoscopy, defecating proctography, pelvic magnetic resonance imaging, and anorectal manometry all were normal. A transit study showed delayed small-bowel emptying. Colonic transit could not be accurately interpreted because of the marked delayed in proximal transit. An ileostomy was being considered to defunction the colon after the patient become desperate for a better quality of life. She also complained of severe urinary frequency and incomplete emptying. A cystoscopy was normal, and a temporary sacral neuromodulation device was inserted as a staged procedure to improve her urinary symptoms. From the day of device placement and thereafter, the patient defecated without difficulty and has also been free of bladder symptoms. Repeat colonic transit has shown normalization of the stomach, small bowel, and colon.

Studying goalies, who play a key position in hockey requires examining psychophysiologic variables and their relationship to performance during games when the outcome is important [15]. This investigation tested all three aspects of emotion (subjective, physiologic changes, and performance). Nine male goalies completed questionnaires and provided salivary cortisol before, during, and after each game. Heart rate (ECG signal) was integrated with the goalie's performance video. Goalies rated on Likert Scales; headaches, stomach aches, insomnia, nervousness, and awareness of heart pounding. Data from 16 games were obtained. Of nine, two goalies provided data on three games each; one goalie was classified as a responder and the other a non-responder, based on salivary cortisol levels (SCL). The responder's SCL increased 572% between baseline and post-period assessments, whereas SCL in the non-responder increased 50% above baseline. The responder's SCL increased 8 times baseline when he faced 16 shots in a period. The responder goalie's game heart rates (HRs) were 160,152, and 167 beats per minute (bpm) and the non-responder's HRs were 147, 132, and 142 bpm for three games. Game performance was similar for both goalies.