KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor.

The KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A-KDM4D), which selectively remove the methyl group(s) from tri/dimethylated lysine 9/36 of H3, modulate transcriptional activation and genome stability. The overexpression of KDM4A/KDM4B in prostate cancer and their association with androgen receptor suggest that KDM4A/KDM4B are potential progression factors for prostate cancer. Here, we report the crystal structure of the KDM4B·pyridine 2,4-dicarboxylic acid·H3K9me3 ternary complex, revealing the core active-site region and a selective K9/K36 site. A selective KDM4A/KDM4B inhibitor, 4, that occupies three subsites in the binding pocket is identified by virtual screening. Pharmacological and genetic inhibition of KDM4A/KDM4B significantly blocks the viability of cultured prostate cancer cells, which is accompanied by increased H3K9me3 staining and transcriptional silencing of growth-related genes. Significantly, a substantial portion of differentially expressed genes are AR-responsive, consistent with the roles of KDM4s as critical AR activators. Our results point to KDM4 as a useful therapeutic target and identify a new inhibitor scaffold.

Bilateral superselective arterial microcoil embolization in post-traumatic high-flow priapism: a case report.

Priapism is a prolonged penile erection unrelated to sexual stimulation. High-flow arteriogenic priapism is uncommon and usually occurs after genitoperineal trauma, which may damage a feeding cavernosal artery, leading to an arteriovenous fistula and, occasionally, to an associated pseudoaneurysm. The defects rarely occur bilaterally. Herein, we report successful treatment of high-flow priapism secondary to a traumatic pseudoaneurysm fed from the bilateral cavernosal artery. Diagnosis was made after cavernosal blood gas analysis, color Doppler ultrasonography, and superselective angiography. Treatment consisted of superselective arterial embolization using metallic microcoils and resulted in simultaneous detumescence of the penis with no complications. The patient regained morning erection on the second postoperative day and erectile function remained normal 8 months after treatment. This case shows that bilateral arteriocavernosal fistulae can be successfully treated with superselective arterial embolization without affecting potency and highlights the importance of warning men about the possibility of developing high-flow priapism following a perineal trauma.

Management of low-flow priapism using the Winter procedure: a case report.

Priapism is a prolonged penile erection that is unrelated to sexual stimulation. Low-flow priapism has been associated with sickle cell disease and other hemoglobinopathies, neoplastic syndrome, anticoagulant therapy, psychotropic medication, and idiopathic causes. We report the successful treatment of idiopathic low-flow priapism using the Winter procedure. Initial treatment consisted of aspiration and intracavernous irrigation with iced saline and a vasoconstrictive agent, but in vain. We then performed the Winter procedure, in which fistulas between the corpora cavernosa and the glans penis were created. This resulted in the simultaneous detumescence of the penis, without complication. The erectile function of the penis was normal 1 year after the procedure. This case shows that idiopathic low-flow priapism can be successfully treated using the Winter procedure when conservative treatment fails.

Leiomyoma of the urinary bladder: a case report.

Leiomyoma of the urinary bladder is a rare tumor and constitutes 35% of benign mesenchymal bladder tumors. Herein, we report a case of leiomyoma of the bladder. A 32-year-old female was incidentally found to have an abnormal bladder mass on abdominal ultrasound during work-up for infertility. Bimanual examination then revealed a mass on the right side near the bladder neck area. On cystoscopic examination, an external compression mass covered with normal bladder mucosa could be seen at the right lateral wall. Computerized tomography revealed a homogeneous solitary tumor protruding into the urinary bladder from the right lateral wall without enlarged lymph nodes. Magnetic resonance imaging showed an intraluminal round mass at the right aspect of the urinary bladder, leading to suspicion of an intramural neurogenic or mesenchymal tumor. Surgical exploration was performed via a lower midline incision and a 5.0 x 4.5 x 2.2 cm mass was excised. The pathologic diagnosis was leiomyoma of the bladder. We discuss the diagnosis and management of leiomyoma of the bladder and briefly review the literature.

Bilateral traumatic testicular dislocation--a case report.

Traumatic testicular dislocation is a rare complication of blunt scrotal trauma. It is usually related to straddle injuries from motorcycle accidents and is commonly accompanied by scrotal hematoma and pelvic fracture. Bilateral dislocation of the testes is relatively rare. We report a rare case of bilateral testicular dislocation after a motorcycle accident. Abdominal computed tomography (CT) and color Doppler ultrasonography are helpful in locating the dislocated testicle and detecting its blood flow. Closed reduction of a superficial testicular dislocation may be attempted first. After appropriate physical examination and image study, emergent surgical reduction should be considered because of the high incidence of failure of closed reduction. We recommend that emergency physicians should be aware of potential testicular injury among trauma cases. Early reduction and early urological consultation are also recommended because of histological changes seen in dislocated testis.

Herpes zoster induced neuropathic bladder--a case report.

Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.