Long-Term Efficacy and Safety of Terazosin in the Symptomatic Treatment of Benign Prostatic Hyperplasia / 대한남성과학회지

PURPOSE: To evaluate the long-term efficacy and safety of terazosin, a selective alpha-1 blocker, in the treatment of benign prostatic hyperplasia (BPH) in Korea. PATIENTS AND METHODS: This was a 24-month, open-label, baseline-controlled study with patients evaluated at 1-to 6-month intervals. A total of 228 male patients aged 50 years or older who had clinical evidence of BPH were enrolled. Terazosin was given starting at 1 mg per day and then maintained at a dose of 3-4 mg daily. Efficacy, as judged by the International Prostate Symptom Score (IPSS), and the blood pressure (BP) were assessed according to the schedule. RESULTS: A total of 126 patients completed the study, with the most common reasons for withdrawal being loss to follow-up or adverse events. The mean IPSS was reduced by 35% or greater. In the hypertensive patients, the mean systolic BP was reduced by 11.9%(-18 mmHg) and the mean diastolic BP by 16.8%(-17 mmHg), whereas in normotensive patients, the reductions were 4.0% (-5 mmHg) and 1.2% (-1 mmHg), respectively. There were no significant differences in the IPSS improvement in these two groups. Forty-nine adverse events were reported by 32 patients, the most common being dizziness, postural hypotension, and headache. CONCLUSION: This study suggests that terazosin is effective and well tolerated in long-term treatment of patients with BPH.

The Experimental Effect of High Intensity Focused Ultrasound (HIFU) being Developed in Korea / 대한비뇨기과학회지

PURPOSE: This project aimed to determine the adequacy and accuracy of high-intensity focused ultrasound(HIFU) for ablating canine model of benign prostate hyperplasia and to assess the therapeutic results. MATERIALS AND METHODS: Using the developed transrectal type HIFU transducer, exposure time-temperature curves were obtained. In-vitro experiments were performed on calf muscle tissues and characteristics of coagulative lesions were observed. In-vivo experiments were performed on canine prostate, which were evaluated grossly, histologically, and ultrasonographically. Complications and side effects were assessed by blood chemistry and urinalysis. RESULTS: The peak temperature reached to 93.0+/-3.0degrees C within initial 11 seconds at the focused area. The mean thermal elevation was 56.0+/-3.0degrees C. In in-vitro HIFU experiments, the coagulative lesions were observed at the focused areas of muscle tissues. The lesions were ellipsoidal shaped, 5.0+/-2.0mm diameter, well delinated. In animal experiments, the affected canine prostates were shown definite lesions of coagulative necrosis which were confirmed grossly and histologically. Significant side effects or complications were not assessed. CONCLUSIONS: Transrectal HIFU treatment may be considered as safe, effective technique on prostate. It is neccessary to perform long-term animal experiments and clinical trials.

Doxazosin in the Symptomatic Treatment of Benign Prostatic Hyperplasia / 대한비뇨기과학회지

PURPOSE: This study set out to investigate the safety and efficacy of doxazosin treatment in symptomatic patients with benign prostatic hyperplasia(BPH) in Korea. MATERIALS AND METHODS: A total of 237 male patients aged 50 or over with clinical evidence of BPH were enrolled into this 12-week, open, baseline-controlled, dose-response study. A run-in period of 2 weeks placebo treatment was followed by 10 weeks of doxazosin treatment. The initial dose was 1mg per day which, at 2-week intervals, could have been titrated up to 2, 4, or 8mg per day. Efficacy, in terms of International Prostate Symptom Score(I-PSS) and blood pressure(BP), was assessed from Week 6 onwards. RESULTS: A total of 180 patients(mean age 65.3 years) completed the study, with the most common reason for withdrawal being lost to follow-up(35 cases); four patients were withdrawn due to adverse events. Mean I-PSS score was reduced by 48.8%(from 21.5 at baseline to 11 at completion). Subset analysis of normo- or hypertensive patients showed that in the 26 hypertensive patients mean systolic BP was reduced by 12.3%(-19mmHg) and mean diastolic BP by 13.7%(-14mmHg), whereas in normotensive patients the reductions were 4.0%(-5mmHg) and 1.9%(-1.5mmHg), respectively. No differences in I-PSS improvements were seen between these two groups. The effects of age were also investigated and showed no significant differences in the changes in blood pressure for older patients(> or =65 years; n=91 ) compared with younger patients(7.5/5.8mmHg compared with 6.5/5.0mmHg). There were no differences in I-PSS improvement. Twenty eight adverse events were reported by 16 patients, the most commomly reported events being dizziness, postural hypotension, and headache. CONCLUSIONS: The effectiveness and safety of doxazosin in the treatment of BPH was confirmed in this Korean population, with significant improvements in I-PSS regardless of patient age and blood pressure at baseline. The baseline I-PSS was higher than is commonly seen in European populations, indicating a greater disease severity.

Relationship between Lower Urinary Tract Symptom and Hypertension: Coprevalence Rate and Symptom Severity / 대한비뇨기과학회지

PURPOSE: It is presumed that lower urinary tract symptom(LUTS) and hypertension are related to the age-dependent sympathetic activity. Thus, the attempt to elucidate a correlation between these two conditions can be important in their management. We investigated the relationship between LUTS and hypertension. MATERIALS AND METHODS: From 1995 to 1997, 1011 men(422 from routine physical checkup, 288 benign prostatic hyperplasia(BPH) patients, 301 hypertension patients) over 50 years were enrolled. The international prostate symptom score(IPSS) and blood pressure were recorded in all. 422 men from physical checkup were grouped into 4 categories according to the presence of LUTS(IPSS> or =8) or hypertension(systolic> or =140mmHg, diastolic> or =90mmHg). The prevalence of hypertension, and the degree of LUTS were evaluated. Statistical analysis was performed with t-test, chi-square test and Mantel-Haenszel test. RESULTS: The prevalence of hypertension was not significantly different between the LUTS(n=177) and non-LUTS groups(n=245)(38.4% vs 35.9%, p=0.600) in men from physical checkup. There was no difference according to age(p=0.513). The prevalence of hypertension was 39.6% in the BPH group(N=288) and was not different compared to the non-LUTS group(n=245)(p=0.385). No significant difference in the prevalence of LUTS was seen between hypertensives(n=156) and normotensives(n=266)(53.2% vs 48.2%, p=0.447) in the physical checkup group. However, their mean IPSS (8.9+/-6.5 vs 7.6+/-5.6) were significantly different(p=0.030). The mean IPSS between hypertensives(15.21+/-4.5) and normotensives(12.75+/-5.0) from the LUTS group(n=178) were significantly different(p=0.002). The mean IPSS of the patients with hypertension(n=301, 9.6+/-5.9) was significantly higher than normotensive men(n=266, 7.6+/-5.6) from physical checkup(p=0.001). CONCLUSIONS: Hypertension and LUTS including BPH do not correlate prevalence-wise, however, hypertension may affect the degree of IPSS.

The loss of expression of transforming growth factor-beta receptors correlates with the histopathologic tumor grade in bladder transitional cell carcinoma patients

Transforming growth factor-beta (TGF-beta), a pleiotropic growth factor, is a potent inhibitor of cellular proliferation in cells of epithelial origin. Recently, it has been suggested that a loss of sensitivity to TGF-beta through a loss of expression of TGF-beta receptors T beta R-I and T beta R-II--is associated with tumor initiation and progression. Therefore, to investigate the relationship between TGF-beta receptors expression and carcinogenesis of bladder TCC, this study examined the expression of T beta R-I and T beta R-II in 46 bladder TCC patients using immunohistochemistry. Since histopathological grade is a widely accepted marker of prognosis, the results were compared in relation to the three grades of bladder TCC. The results demonstrated that the loss of TGF-beta receptors expression is associated with increasing histopathological grades of bladder TCC. Specifically, both T beta R-I and T beta R-II were readily detected in all 10 normal bladder mucosa specimens. Likewise, all 6 specimens of grade I TCC samples expressed high levels of both TGF-beta receptors. However, among grade II TCC samples, T beta R-I and T beta R-II were detected in 78% and 89%, respectively: among grade III TCC samples, T beta R-I and T beta R-II were detected in 45% and 41%, respectively. These results suggested that loss of sensitivity to TGF-beta may play a role in the progression of TCC from low to high grade disease.

Effect of Synthetic Tyrosine Kinase Inhibitor(ZM260603) on the Growth of Prostate Cancer Cell Lines: Differences According to Androgen Dependency and Bcl-2 Expression / 대한비뇨기과학회지

PURPOSE: We determined the effect of tyrosine kinase inhibitor(TKI), ZM260603 on the growth of prostate cancer cell lines. MATERIALS AND METHODS: Using the synthetic TKI, ZM260603, cytotoxicity test and cell cycle analysis were performed on LNCaP, DU-145 and PC3 prostate cancer cell lines. The bcl-2 and bax protein expressions were observed in PC3 prostate cancer cell line by western blotting. The inhibitory effect of TKI was determined under the presence or absence of dehydrotestosterone, in androgen-dependent LNCaP prostate cancer cell line. RESULTS: The synthetic TKI, ZM260603 showed definite cytotoxicity on all prostate cancer cell lines studied regardless of androgen-dependency. The IC50 were 0.35+/-0.08microM, 0.12+/-0.06microM and 0.21+/-0.09microM for LnCaP, DU-145 and PC-3 cell lines, respectively. The G0/G1 phase arrests were observed commonly in all of these cell lines by flowcytometric analysis. Decrement in bcl-2 expression and increment of bax protein expression in the PC-3 cell line was observed by western blotting. The IC50 of hormone-dependent LNCaP prostate cancer cell line on TKI was increased about four folds by the addition of dihydrotestosterone. CONCLUSIONS: Our results suggest that the changes in the expression of bcl-2 and bax proteins are related with inhibitory process of the synthetic TKI, ZM260,603 on the growth of prostate cancer cell lines. Androgen seems to act as compromising or weakening the effects of TKI in androgen-dependent prostate cancer cell line, although the exact relationships between androgen-dependency and bcl-2 expression are unclear.