Development and progression of prostate cancer are intimately associated with androgen receptor (AR) signaling. The emergence of hormone-refractory prostate cancer and consequent failure of conventional androgen deprivation therapies make it necessary to bypass hormonal resistance by targeting the same signaling pathway at new intervention points. In our study, we showed that cryptotanshinone inhibited the growth of AR-positive prostate cancer cells, suggesting that cryptotanshinone affected AR function. Cryptotanshinone also profoundly inhibited the transcriptional activity of AR and suppressed the expression of several AR-target genes at the mRNA and the protein levels. At the molecular level, cryptotanshinone disrupted the interaction between AR and lysine-specific demethylase 1 (LSD1), and inhibited the complex of AR and LSD1 to the promoter of AR target genes without affecting the protein degradation and translocation of AR. Cryptotanshinone increased the monomethyl and di-methylation of Histone H3 lysine 9 (H3K9), a repressive histone marker which is demethylated and activated by LSD1. These data suggest that cryptotanshinone functions via inhibition of LSD1, a protein that promotes AR-dependent transcriptional activity via derepression of H3K9. In summary, we describe a novel mechanism whereby cryptotanshinone downregulates AR signaling via functional inhibition of LSD1-mediated demethylation of H3K9 and represses the transcriptional activity of AR. Our data suggest that cryptotanshinone can be developed as a potential therapeutic agent for prostate cancer.

Bone metastasis is the major cause of mortality associated with prostate cancer. Whereas activin A is known to inhibit prostate cancer cell growth and promote apoptosis, the correlation of elevated activin A with increasing serum prostate-specific antigen (PSA) levels in bone metastatic stages of prostate cancer is well documented. The molecular mechanisms explaining these paradoxical effects of activin A and how activin A influences the progression of prostate cancer with bone metastasis remain unclear. By comparing expression profiles of primary prostate cancer biopsies, with and without bone metastasis, we discovered that the expression of activin A is increased in cases with bone metastatic propensity and correlates with increased androgen receptor (AR), PSA expression, and Gleason scores. Activin A promotes migration of prostate cancer cells to osteoblasts, elevates the AR gene transcription through Smads through binding to AR promoter, and induces nuclear translocation of AR to interact with Smad3. Knockdown of Smad3 by siRNA decreases activin A-promoted AR expression and cancer cell migration. Overexpression of AR reversed Smad3-siRNA suppression on activin A-mediated cell migration to osteoblasts. These data suggest that activation of the AR through Smads is required for activin A-promoted prostate cancer cell migration to bone matrix, thereby promoting the bone metastatic phenotype, and the activin A-Smad-AR axis may be considered a therapeutic target in bone metastatic diseases.

Due to the dielectric constant of traditional FR4 substrate is lower (ε r =4.2); it is not suitable for the fabrication of small size microwave antennas. In order to reduce the size of the fabricated antennas, the ceramics with higher dielectric constant can be used as the substrates of the designed patch antenna. In this paper, the designed patch antenna is printed on Aluminum Oxide (Al 2 O 3 , ε r =9.8). Due to larger dielectric constant of Al 2 O 3 ceramic, the size of the designed patch antenna can be reduced to about 25mm × 32mm. It is found that the patch size and the length of transmission line will influence the return loss (S 11 ) and the resonant frequency of the fabricated patch antennas. The optimum bandwidth of the designed antenna can reach 400MHz/16.3%, the resonance frequency is near 2.45GHz, and the S 11 is −31dB. KEYWORDS: patch antenna, Al 2 O 3 , monopole antenna IntroductionIn the past years, the communication devices had been rapid developments in wireless local area network (WLAN) applications. To satisfy the 2.4GHz band of IEEE 802.11b and 5.2GHz band of IEEE 802.11a WLAN standards, dual operations in the 2.4GHz (2.4-2.484GHz) and 5.2GHz (5.15-5.35GHz) bands were demanded in practical WLAN applications. A small size antenna was highly desirable because the size of communication devices was decreased. The antenna should be designed in planar form to match the rapid development in wireless communication applications. For WLAN, the requirement of single-band antenna were also necessary for many applications, so printed monopole antennas with single-band operation were still in great demand [1].Recently, printed monopole antennas played an important role in wireless technology. The main reasons were low cost, small size, light weight, easy realization, and reasonably good performance, respectively [2]. Therefore, printed microstrip patch and slot antennas had the potential to meet the above requirements due to their inherently planar structures. There