Recombinant human interleukin-2, 125Ala(Beijing SL Pharmaceutical Co., Ltd.)

Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies of prostate cancer (PCa) have shown anti‐tumor activity with digoxin. We explore the relationship between use of digoxin and PCa risk.

Data from a population‐based case–control study of incident cases aged 35–74 years at PCa diagnosis in 2002–2005 in King County, Washington were available. Controls were identified by random digit dialing and frequency matched by age. Use of digoxin was determined from in‐person questionnaires regarding medical and prescription history. The relationship of digoxin use with PCa risk was evaluated with logistic regression.

One thousand one cases of PCa and 942 controls were analyzed. The prevalence of digoxin use in controls was 2.7%, and use was positively correlated with age. In multivariate analysis adjusting for age, race, PSA screening, and family history of PCa, digoxin use was associated with a reduction in the odds ratio of PCa (OR 0.58, 95% CI: 0.30–1.10). Among those with ≥3 PSA tests over the preceding 5 years (546 cases, 380 controls), digoxin use was associated with a stronger reduction of PCa risk (OR 0.44, 95% CI: 0.20–0.98).

These data indicate digoxin use may be associated with a reduction in risk of PCa. Given the potential mechanisms by which digoxin may exert an anti‐neoplastic effect and other recent studies showing a negative association between digoxin use and PCa, further research is warranted. Prostate 74:97–102, 2014. © 2013 Wiley Periodicals, Inc.

Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (≤12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, muscles were harvested or injured with cardiotoxin and collected at 3, 5, or 14 days thereafter. When compared with Control, Xin-shRNA infection attenuated muscle regeneration as demonstrated by Myh3 expression and fiber areas. Given the colocalization of Xin and MyoD, we isolated single myofibers from infected muscles to investigate the effect of silencing Xin on SC function. Relative to Control, SC activation, but not proliferation, was significantly impaired in Xin-shRNA-infected muscles. To determine whether Xin affects the G0-G1 transition, cell cycle reentry was assessed on infected C2C12 myoblasts using a methylcellulose assay. No difference in reentry was noted between groups, suggesting that Xin contributes to SC activation by means other than affecting G0-G1 transition. Together these data demonstrate a critical role for Xin in SC activation and reduction in Xin expression results in attenuated skeletal muscle repair.