Yu-Wei Lai

Inhibitory Effects of Butein on Cancer Metastasis and Bioenergetic Modulation

Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment.

Effectiveness of stress management in patients undergoing transrectal ultrasound-guided biopsy of the prostate.

Background To assess the utilization of stress management in relieving anxiety and pain among patients who undergo transrectal ultrasound (TRUS)-guided biopsy of the prostate. Methods Eighty-two patients admitted to a community hospital for a TRUS biopsy of the prostate participated in this case-controlled study. They were divided into an experimental group that was provided with stress management and a control group that received only routine nursing care. Stress management included music therapy and one-on-one simulation education. Before and after the TRUS biopsy, the patients’ state-anxiety inventory score, pain visual analogue scale (VAS), respiratory rate, heart rate, and blood pressure were obtained. Results There were no differences in baseline and disease characteristics between the two groups. The VAS in both groups increased after the TRUS biopsy, but the difference in pre- and postbiopsy VAS scores was significantly lower in the experimental group (P=0.03). Patients in both groups experienced mild anxiety before and after the biopsy, but those in the experimental group displayed a significantly greater decrease in postbiopsy state-anxiety inventory score compared to the control group (P=0.02). Conclusion Stress management can alleviate anxiety and pain in patients who received a TRUS biopsy of the prostate under local anesthesia.

Varicocele is associated with varicose veins: A population‐based case–control study

To analyze the association between patients with varicocele and varicose veins in Taiwan.

BMP-2 induces angiogenesis by provoking integrin α6 expression in human endothelial progenitor cells.

Graphical abstract Figure. No Caption available. Abstract Bone morphogenetic protein‐2 (BMP‐2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP‐2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found that BMP‐2 promoted cell migration and tube formation of EPCs in a concentration‐dependent manner, indicating BMP‐2 induced in vitro angiogenesis in human EPCs. Furthermore, BMP‐2 significantly increased microvessel formation in Matrigel plug assay, and BMP‐2 antagonist noggin prevented BMP‐2‐induced in vivo angiogenesis. Mechanistic investigations showed BMP‐2 profoundly induced the expression of Id‐1 and integrin &agr;6 as well as EPCs angiogenesis by activating PI3K/Akt and MEK/ERK signaling pathways. Moreover, knockdown of Id‐1 and integrin &agr;6 by siRNA transfection obviously attenuated BMP‐2‐indueced tube formation of EPCs. These results suggest that BMP‐2 promotes angiogenesis in human EPCs through the activation of PI3K/Akt, MEK/ERK, and Id‐1/integrin &agr;6 signaling cascades. This is the first demonstration that BMP‐2 exhibits the angiogenesis property on human EPCs. BMP‐2 might serve as the potential therapeutic target for treatment of angiogenesis‐related diseases.

CCN3 promotes epithelial-mesenchymal transition in prostate cancer via FAK/Akt/HIF-1α-induced Twist expression

Epithelial-mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining metastatic behavior during cancer progression. NOV/CCN3 is a matrix-associated protein involved in many cellular functions. Previous studies have shown that CCN3 expression is upregulated in prostate cancer (PCa) cells and in PCa patients. In this study, we have provided evidence of tumor promoting effects of CCN3, which includes induction of epithelial-to-mesenchymal transition (EMT) and tumor metastasis. We used an orthotopic in vivo model to demonstrate the prometastatic effects of CCN3. Overexpression or knockdown of CCN3 changed the EMT phenotype in PCa cells. Moreover, treatment with recombinant CCN3 promoted EMT in PCa cells. We also found that CCN3 may promote EMT by activating the FAK/Akt/HIF-1α pathway and this activation is responsible for Twist expression. IHC staining confirmed a positive correlation between the expression of CCN3, Twist, and tumor stage in PCa tissue. Our findings provide insight into the involvement of CCN3 in the EMT regulation of prostate cancer. CCN3 is a promising molecular target that may contribute to a novel therapeutic strategy against metastatic PCa.

Nationwide survey to evaluate medical utilization by patients with inguinal hernia and the risk of developing varicocele in Taiwan

Background The purpose of this study was to analyze age, geographical and seasonal variations in medical service utilization by patients with inguinal hernia in Taiwan, and the influence of herniorrhaphy on development of ipsilateral varicocele in male patients. Methods Between 2001 and 2008, comprehensive data on the characteristics of medical service utilization by patients with inguinal hernia was evaluated via a retrospective nationwide population-based study. Data were obtained from the National Health Insurance Research Database in Taiwan. Parameters for comparison included newly diagnosed inguinal hernia cases, number of herniorrhaphies, and incidence rates every year, number of outpatient visits for inguinal hernia, and herniorrhaphy by age, season, and area of Taiwan. Results There was an average of 1,466 newly diagnosed inguinal hernia cases and 871.9 herniorrhaphies performed per year per million population during the study period. The male ratio for both newly diagnosed inguinal hernia cases and number of herniorrhaphies increased significantly by age. The number of newly diagnosed inguinal hernia cases and outpatient visits for inguinal hernia was highest during summer, followed by spring, autumn, and winter, and in the north of Taiwan, followed by the center, south, and east. Additionally, the incidence of developing ipsilateral varicocele after herniorrhaphy was low in male patients. Conclusion The number of newly diagnosed inguinal hernia cases and outpatient visits for inguinal hernia is highest during summer and lowest in eastern Taiwan. In addition, the incidence of developing ipsilateral varicocele after herniorrhaphy is higher in patients aged 10–19 years.