Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge / 中国结合医学杂志

OBJECTIVE@#To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo.@*METHODS@#Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured.@*RESULTS@#Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth.@*CONCLUSION@#SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

Electromagnetic Low-Intensity Extracorporeal Shock Wave Therapy in Patients with Erectile Dysfunction: A Sham-Controlled, Double-Blind, Randomized Prospective Study

PURPOSE: The aim of the present study was to evaluate the efficacy and safety of the electromagnetic-type low-intensity extracorporeal shock wave therapy (Li-ESWT) in patients with erectile dysfunction (ED).MATERIALS AND METHODS: The randomized, sham-controlled, double-blind prospective study was performed at two referral hospitals. Participants were randomized in a 1:1 ratio to receive sham or Li-ESWT for 6 weeks. ED was evaluated at screening and at 4 and 7 weeks after treatment. Participants were asked to complete the international index of erectile function-erectile function (IIEF-EF) domain questionnaire, erection hardness scale (EHS), and sexual encounter profile questionnaire (SEPQ 2 and 3). The development of complications was investigated.RESULTS: Eighty-one of 96 patients completed the study. The median change in the IIEF-EF score in the Li-ESWT and sham groups was 5.1 and −2.2 (p<0.001), respectively, at the 7-week follow-up; 47.4% (18/38) patients had EHS <3, of which 77.8% (14/18) showed significant improvement in virtue of Li-ESWT treatment (p=0.001). A significant improvement was observed in the percentage of “Yes” responses to SEPQ 2 and 3 in the Li-ESWT group vs. sham group from baseline to 7-week follow-up (91.3% vs. 69.4%; p=0.008 and 50.0% vs. 14.3%; p=0.002, respectively). No patients reported pain or other adverse events during treatment or follow-up.CONCLUSIONS: Thus, Li-ESWT could have a role in improving erectile function. Furthermore, it is safe. We believe that Li-ESWT is an attractive new treatment modality for patients with ED.

Effect of Korean Herbal Formula (Modified Ojayeonjonghwan) on Androgen Receptor Expression in an Aging Rat Model of Late Onset Hypogonadism

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

PURPOSE: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. MATERIALS AND METHODS: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. RESULTS: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05). CONCLUSIONS: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.

Changes in Nocturia and Lower Urinary Tract Symptoms after Radical Prostatectomy

PURPOSE: The goal of this study was to evaluate changes in nocturia and other lower urinary tract symptoms (LUTS) after laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We reviewed the medical records of 96 patients who underwent LRP or RALP for clinically localized prostate cancer and completed the International Prostate Symptom Score (IPSS) questionnaire, which provided a basis for assessing their symptoms. We also evaluated maximal flow rate and post-void residual urine volume over a follow-up period of at least 24 months. We divided the patients into three groups according to postoperative changes in the frequency of nocturia. RESULTS: Voiding symptoms significantly improved over the course of 24 months in patients who underwent LRP or RALP. However, most patients showed persistent or increased nocturia after LRP or RALP. Moreover, more than one third of the patients (33/96) presented with exacerbated nocturia (1.0+/-0.9 episodes of preoperative nocturia vs. 3.0+/-1.3 episodes of postoperative nocturia). Multiple regression analysis showed that preoperative IPSS storage sub-score had negative association with the nocturia after radical prostatectomy (p=0.005). However, patients' age, body mass index, preoperative prostate specific antigen, Gleason score, T-stage, and prostate volume had no association. CONCLUSIONS: The present study showed that nocturia was influenced by a range of factors, including other storage LUTS and the relief of bladder outlet obstruction after radical prostatectomy. Moreover, the preoperative storage symptoms are regarded as an important factor which influences the changes of nocturia after radical prostatectomy.

Effect of Korean Red Ginseng on Testicular Tissue Injury after Torsion and Detorsion

PURPOSE: Korean red ginseng (KRG) is a potent antioxidant and a free radical scavenger. This study was designed to determine whether KRG could protect against dysfunction and oxidative stress induced by torsion-detorsion injury in rat testis. MATERIALS AND METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into four groups: a sham-operated control group (C), a sham-operated and KRG-treated group (K), a 2 hours torsion and detorsion group (T), and a 2 hours torsion and detorsion and KRG-treated group (T+K). We measured testis weight and hormone levels and reactive oxygen species (ROS) from the left renal vein. Superoxide generation was measured on the basis of lucigenin-enhanced chemiluminescence in testis tissue. RESULTS: Testicular weight was significantly higher in the T+K group than in the T group; however, there were no significant differences in hormone levels between the 4 groups. The mean level of ROS and superoxide production was significantly higher in the T group than in the C group, whereas administration of KRG attenuated this increase. Upon histologic evaluation, the T group was found to have cellular disarray, a lack of cellular cohesiveness, degenerative changes in the germinal cells, and less distinct changes in the seminiferous tubules, whereas the T+K group had a germinal epithelial layer that appeared nearly normal. CONCLUSIONS: The present study demonstrated that KRG recovered the testis dysfunction in the rat testis by suppressing superoxide production.

Early Experience of Prostate Cancer Treated with CyberKnife(TM) Radiotherapy

PURPOSE: We investigated the outcome in patients with prostatic cancer treated by means of CyberKnife(TM) radiotherapy. MATERIALS AND METHODS: Between July 2007 and April 2009, 16 patients with prostate cancer underwent CyberKnife(TM) radiotherapy. The histologic diagnosis was established by transrectal ultrasonography-guided biopsy. Radiotherapy was performed for a dose of 34 Gy at 8.5 Gy per day over 4 to 18 days. Nine patients were treated with hormone therapy. After treatment, prostate-specific antigen (PSA) relapse was evaluated with periodic PSA follow-up. RESULTS: The numbers of patients in clinical stages T2 and T3 were 13 and 3, respectively. Two patients had lymph node metastasis with no distant metastasis. The numbers of patients with a Gleason grade of 5, 6, 7, 8, and 9 were 1, 5, 4, 3, and 2, respectively. The mean time to PSA nadir and the mean PSA at nadir were 7 months and 0.43 ng/ml, respectively. To date, there has been no biochemical failure or clinical recurrence. No severe complications were observed in any patients; observed minor complications [n (%)] were perianal pain [2 (12.5%)] and defecation discomfort [2 (12.5%)]. CONCLUSIONS: Generally good responses were observed in patients treated with CyberKnife(TM) radiotherapy for prostate cancer. No severe complications were observed. More patients and a longer follow-up are required for further conclusions.

Efficacy of Laparoscopic Ureterolithotomy for the Upper Ureter Stone / 대한비뇨기과학회지

PURPOSE: Ureter stones are the most common urological disease. The principal objective of this study was to evaluate the results, efficacy, and safety rates of laparoscopic ureterolithotomy for the treatment of large, upper ureteral stones. MATERIALS AND METHODS: Between April 2006 and February 2008, we conducted laparoscopic ureterolithotomy in 7 patients with upper ureter stones(L2-3). Laparoscopic ureterolithotomy was conducted in 5 patients as a salvage procedure after failed shock wave lithotripsy, in 1 patient as the primary procedure for a large stone(28mm), and in 1 patient for treatment of a radiolucent matrix stone. Laparoscopic ureterolithotomy was conducted via a transperitoneal approach. The mean stone size was 20.7+/-5.9mm. RESULTS: Laparoscopic ureterolithotomy was successful in 7 patients, and none of the patients required an open procedure. All patients were rendered stone-free after a single procedure. The mean operative duration, mean postoperative hospital stay, and mean estimated blood loss were 142+/-49 min, 6+/-2.2 days and 85+/-29.5ml, respectively. CONCLUSIONS: Although the majority of patients with ureter stones can be rendered stone-free via shock wave lithotripsy and endourological procedures, open surgery is required for large and upper ureter stones. In cases of large and upper ureter stones, laparoscopic ureterolithotomy may be considered for a limited group, although many will require open surgery.