Peyronie’s Disease: Current Medical Treatment and Future Perspectives

류지간,서준규 대한비뇨의학회 2009 Investigative and Clinical Urology Vol.50 No.6

Purpose: Because of our incomplete understanding of the pathogenesis of Peyronie’s disease (PD), management of PD remains a therapeutic dilemma in the field of sexual medicine. Most currently available medical treatments have not demonstrated conclusive effects. The present review addresses the current status of nonsurgical treatment and emerging new therapeutic targets for PD. Materials and Methods: A systematic review of clinical or preclinical results of nonsurgical treatment for PD published as original articles in peer-reviewed journals is provided. Results: Although many studies regarding nonsurgical treatment of PD showed positive outcomes, the majority of these studies were not placebo-controlled approaches. Currently available randomized controlled trials on the use of oral, intralesional injection, and topical agents have not showed conclusive effects, with minor or little effect. However, the outcomes of recent preclinical studies targeting the TGF-β pathway or NO-cGMP pathway are promising. Conclusions: There is no viable therapeutic option for PD between watchful waiting and surgical manipulation. With further research into the pathologic cascade of cellular and molecular events and an increase in our understanding of the pathophysiology of PD using animal models, the development of novel and effective medical therapies will become a realistic objective. Purpose: Because of our incomplete understanding of the pathogenesis of Peyronie’s disease (PD), management of PD remains a therapeutic dilemma in the field of sexual medicine. Most currently available medical treatments have not demonstrated conclusive effects. The present review addresses the current status of nonsurgical treatment and emerging new therapeutic targets for PD. Materials and Methods: A systematic review of clinical or preclinical results of nonsurgical treatment for PD published as original articles in peer-reviewed journals is provided. Results: Although many studies regarding nonsurgical treatment of PD showed positive outcomes, the majority of these studies were not placebo-controlled approaches. Currently available randomized controlled trials on the use of oral, intralesional injection, and topical agents have not showed conclusive effects, with minor or little effect. However, the outcomes of recent preclinical studies targeting the TGF-β pathway or NO-cGMP pathway are promising. Conclusions: There is no viable therapeutic option for PD between watchful waiting and surgical manipulation. With further research into the pathologic cascade of cellular and molecular events and an increase in our understanding of the pathophysiology of PD using animal models, the development of novel and effective medical therapies will become a realistic objective.

풍선박리기구를 이용한 복막외 복강경수술

류지간,박동수,양승철 大韓泌尿器科學會 1996 Korean Journal of Urology Vol.37 No.4

Gas 주입없이 시행한 복막외 복강경수술

류지간,양승철 大韓泌尿器科學會 1996 Korean Journal of Urology Vol.37 No.4

Korean Society for Sexual Medicine and Andrology (KSSMA) Guideline on Erectile Dysfunction

류지간,조강수,김수진,오경진,감성철,서경근,신홍석,김수웅 대한남성과학회 2013 The World Journal of Men's Health Vol.31 No.2

In February 2011, the Korean Society for Sexual Medicine and Andrology (KSSMA) realized the necessity of developing a guideline on erectile dysfunction (ED) appropriate for the local context, and established a committee for the development of a guideline on ED. As many international guidelines based on objective evidence are available, the committee decided to adapt these guidelines for local needs instead of developing a new guideline. Considering the extensive research activities on ED in Korea, data with a high level of evidence among those reported by Korean researchers have been collected and included in the guideline development process. The latest KSSMA guideline on ED has been developed for urologists. The KSSMA hopes that this guideline will help urologists in clinical practice.

Therapeutic Angiogenesis as a Potential Future Treatment Strategy for Erectile Dysfunction

류지간,서준규 대한남성과학회 2012 The World Journal of Men's Health Vol.30 No.2

The cavernous endothelium plays a crucial role in regulating the tone of the underlying smooth muscle and physiologic penile erection. Recently, the link between erectile dysfunction (ED) and cardiovascular disease was unveiled, and the main etiology of ED was found to be vasculogenic. Although oral phosphodiesterase-5 inhibitors are generally effective for men with ED, such therapies do not cure underlying vasculopathy in the corpus cavernosum tissue. This review addresses current preclinical protein, gene, and cell or stem cell therapies for enhancing cavernous endothelial regeneration and restoring erectile function.

Transforming Growth Factor-β1을 발현하는 아데노바이러스를 이용한 음경해면체섬유화 동물모델의 확립

류지간,오승민,Hai Rong Jin,김도경,강용진,장진혁,서준규 대한남성과학회 2010 The World Journal of Men's Health Vol.28 No.2

Purpose: Transforming growth factor-β1 (TGF-β1) has been implicated in cavernous fibrosis due to a variety of causes of erectile dysfunction (ED), such as diabetes mellitus and post-radical prostatectomy. To examine the role of the TGF-β signaling pathway in cavernous fibrosis, we established a rat model of cavernous fibrosis by using adenovirus expressing TGF-β1 (ad-TGF-β1). Materials and Methods: Four-month-old male Sprague-Dawley rats received intracavernous injection of ad-TGF-β1 (1×108, 1×109, or 1×1010 virus particles [vp] in 100 μl of PBS) and the penis was harvested for histologic examination at 10, 20, or 30 days after injection (n=4 per group and per time point). Based on the initial findings, the animals were divided into three groups (n=6 per group): Group 1, age-matched control; Group 2, intracavernous injection of ad-LacZ (1×1010 vp/100 μl); and Group 3, intracavernous injection of ad-TGF-β1 (1×1010 vp/100 μl). At 30 days after injection, erectile function was evaluated during electrical stimulation of the cavernous nerve. The penis was then harvested and stained with Masson’s trichrome and antibody to smooth muscle α-actin. Results: Masson’s trichrome staining revealed that intracavernous delivery of ad-TGF-β1 sufficiently induced cavernous fibrosis in a dose-dependent manner. The fibrotic scars persisted up to 30 days after injection at the highest dosage (1×1010 vp/100 μl), whereas no histologic evidence of cavernous fibrosis was found in the control rats or the ad-LacZ-injected rats. The rats receiving ad-TGF-β1 showed a higher cavernous collagen content and less smooth muscle content than the control rats or ad-LacZ-injected rats. Erectile function was significantly decreased in rats receiving ad-TGF-β1 compared with that in controls or rats receiving ad-LacZ. Conclusions: This model induced by ad-TGF-β1 may play an important role in understanding the pathophysiologic mechanisms of cavernous fibrosis-associated TGF-β signaling and the development of new therapeutics targeting this pathway.

Transforming Growth Factor-β Type I Receptor Inhibitor Induces Functional and Morphologic Recovery in a Rat Model of Erectile Dysfunction and Cavernous Fibrosis

류지간,Jun Kyu Suh,Seung Min Oh,Hai Rong Jin,송강문,Mi Hye Kwon,Do Kyung Kim 대한남성과학회 2012 The World Journal of Men's Health Vol.30 No.1

Purpose: To examine the effectiveness of small-molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor, an activin receptor-like kinase 5 (ALK5), on erectile dysfunction (ED) in a rat model of cavernous fibrosis, in which fibrosis was induced by intracavernous injection of adenovirus expressing TGF-β1 (Ad-TGF-β1). Materials and Methods: Four-month-old Sprague-Dawley rats were divided into four groups (n=10 per group): age-matched controls without treatment, age-matched controls receiving intracavernous injection of LacZ adenovirus, and cavernous fibrosis rats receiving an intracavernous injection of saline or ALK5 inhibitor (5 mg/kg). ALK5 inhibitor or saline was administered on day 5 after injection of Ad-TGF-β1. On day 30, erectile function was assessed by electrical stimulation of the cavernous nerve and the penis was then harvested for histologic studies (n=6 per group) and for the measurement of the hydroxyproline level (n=4 per group). Results: Ad-TGF-β1-induced cavernous fibrosis rats treated with saline showed a significant decrease in cavernous smooth muscle and endothelial content, and an increase in collagen deposition, which resulted in profound deterioration of all erectile function parameters, such as the ratios of maximal intracavernous pressure (ICP), total ICP, and slope to mean arterial pressure. ALK5 inhibitor significantly restored erectile function in a rat model of cavernous fibrosis by increasing cavernous smooth muscle and endothelial content, and by blocking cavernous fibrosis. Conclusions: The results suggest that inhibition of the TGF-β pathway is a promising therapeutic strategy for the treatment of ED related to cavernous fibrosis from various causes.

요석에서 Therasonic LTS와 SDS-5000 기종을 이용한 체외충격파쇄석술의 치료성적

강석찬,류지간,윤상민 대한비뇨의학회 2005 Investigative and Clinical Urology Vol.46 No.3

Purpose: We compared the clinical efficacy of Therasonic LTS(piezoelectric type) with that of SDS-5000 (spark gap type) for the management of urinary stones. Materials and Methods: We evaluated 516 patients treated with Therasonic LTS, between June 1996 and April 2001, and 314 treated with SDS-5000 between September 2001 and January 2003. We compared the average success rates and shock wave sessions according to the stone sizes and locations, and also verified the complications related to the therapies. Results: The total success rates of Therasonic LTS and SDS-5000 were similar(92.6 and 94.6%, respectively), with no difference according to stone location and size. However, the average shock wave sessions were significantly lower in the group treated with SDS-5000(2.5±1.8 sessions) compared to the group treated with Therasonic LTS(3.1±1.9 sessions)(p<0.05). The cumulative success rates were 64.3 and 77.1%, respectively, at the completion of session 3, and 82.2 and 88.2%, respectively, at the completion of session 5. The complication rates associated with the therapies were 8.9 and 6.9%, respectively, consisting of pain, gross hematuria, steinstrasse and acute pyelonephritis, most of which were successfully controlled by conservative treatment. Conclusions: SDS-5000 lithotripsy is more efficient than Therasonic LTS in terms of shock wave sessions.

Regenerative therapies as a potential treatment of erectile dysfunction

정두용,류지간,윤국남 대한비뇨의학회 2023 Investigative and Clinical Urology Vol.64 No.4

Erectile dysfunction (ED) is the most common sexual dysfunction disease in adult males. ED can be caused by many factors, such as vascular disease, neuropathy, metabolic disturbances, psychosocial causes, and side effects of medications. Although current oral phosphodiesterase type 5 inhibitors can achieve a certain effect, they cause temporary dilatation of blood vessels with no curative treatment effects. Emerging targeted technologies, such as stem cell therapy, protein therapy, and low-intensity extracorporeal shock wave therapy (Li-ESWT), are being used to achieve more natural and long-lasting effects in treating ED. However, the development and application of these therapeutic methods are still in their infancy, and their pharmacological pathways and specific mechanisms have not been fully discovered. This article reviews the preclinical basic research progress of stem cells, proteins, and Li-ESWT therapy, as well as the current status of clinical application of Li-ESWT therapy.

Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in Fibroblasts Derived from Peyronie’s Plaque

장진혁,류지간,서준규 대한비뇨의학회 2012 Investigative and Clinical Urology Vol.53 No.1

Purpose: Transforming growth factor-b1 (TGF-b1) is the key fibrogenic cytokine associated with Peyronie’s disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-b type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. Materials and Methods: Plaque tissue from a patient with PD was used for primary fibroblast culture, and we then characterized primary cultured cells. Fibroblasts were pretreated with IN-1130 (10 mM) and then stimulated with TGF-b1 protein (10 ng/ml). We determined the inhibitory effect of IN-1130 on TGF-b1-induced phosphorylation of Smad2 and Smad3 or the nuclear translocation of Smad proteins in fibroblasts. Western blot analyses for plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV were performed to evaluate effect of IN-1130 on the production of extracellular matrix proteins. Results: The treatment of fibroblasts with TGF-b1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-b1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-b1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. Conclusions: Overexpression of TGF-b and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-b signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD. Purpose: Transforming growth factor-b1 (TGF-b1) is the key fibrogenic cytokine associated with Peyronie’s disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-b type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. Materials and Methods: Plaque tissue from a patient with PD was used for primary fibroblast culture, and we then characterized primary cultured cells. Fibroblasts were pretreated with IN-1130 (10 mM) and then stimulated with TGF-b1 protein (10 ng/ml). We determined the inhibitory effect of IN-1130 on TGF-b1-induced phosphorylation of Smad2 and Smad3 or the nuclear translocation of Smad proteins in fibroblasts. Western blot analyses for plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV were performed to evaluate effect of IN-1130 on the production of extracellular matrix proteins. Results: The treatment of fibroblasts with TGF-b1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-b1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-b1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. Conclusions: Overexpression of TGF-b and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-b signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD.