The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3’-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the threedimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3’-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the threedimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) regulates cell growth and tumorigenesis in various cancers. However, the clinical relevance of ERRγ to hepatocellular carcinoma (HCC) remains unclear. Here we examined the clinical significance of ERRγ in HCC and its potential as a therapeutic target. ERRγ levels in tissues from completely resected specimens from 190 HCC patients were examined immunohistochemically and their association with clinical stage and pathological grade was analyzed. Small interfering RNA (siRNA)-mediated knockdown of ERRγ (siRNA-ERRγ) or an ERRγ inverse agonist, GSK5182, were also used to examine the effects of ERRγ inhibition on the proliferation and growth of a human hepatoma cell line, PLC/PRF/5. Immunohistochemical analysis revealed that tumor tissues showed higher levels of ERRγ-positivity than adjacent non-tumor lesions. Tumors showing high levels of ERRγ immunoreactivity also had advanced tumor node metastasis (TNM) and Barcelona Clinic Liver Cancer stages and a higher Edmondson–Steiner grade. In addition, high-level expression of ERRγ in tumors of advanced TNM stage correlated with poorer overall survival. Treatment of PLC/PRF/5 cells with siRNA-ERRγ or GSK5182 inhibited proliferation through G1 arrest, increased expression of p21 and p27 and decreased expression of phosphorylated retinoblastoma protein. GSK5182-induced reactive oxygen species also suppressed the proliferation of PLC/PRF/5 cells. The present study showed that ERRγ expression is clinically significant in HCC; therefore, it can be considered a biomarker for HCC diagnosis. Moreover, the results provide a rationale for the use of ERRγ inhibitors such as GSK5182 as potential therapeutic agents.
Carcinogenesis ; Carcinoma, Hepatocellular ; Cell Line ; Cell Proliferation* ; Child ; Child, Orphaned ; Diagnosis ; Humans ; Liver Neoplasms* ; Liver* ; Neoplasm Metastasis ; Reactive Oxygen Species ; Retinoblastoma Protein ; RNA, Small Interfering

Prostate cancer is the most common type of male cancer worldwide. Although radical prostatectomy (RP) is advised for prostate cancer in patients with a life expectancy of more than 10 years by various guidelines, most elderly men still do not undergo the procedure regardless of increasing life expectancy. This study aimed to determine whether RP is suitable for patients with prostate cancer aged 75 years or older. A retrospective study of patients who underwent RP at 6 institutions between 2005 and 2012 was conducted. Patients were divided into 2 groups at the time of surgery: 65-69 years (younger group) and 75 years or older (older group). We compared clinical characteristics, pathological results, complication rates, and recurrence-free survival between the two groups. Compared with the younger group, the older group had significantly higher preoperative serum prostate-specific antigen level, pre- and postoperative Eastern Cooperative Oncology Group (ECOG) performance status grade, hypertension prevalence, and Gleason score at biopsy and RP. However, except urinary incontinence, there were no statistically significant differences in the peri- and post-operative complications. After median follow-up periods of 36 months (younger group) and 40 months (older group), the biochemical recurrence-free survival rates were not significantly different (P = 0.581). Although the urinary incontinence rate was higher in the older group, RP was a suitable option for selected Korean men aged 75 years or older with limited complication rates and excellent outcomes similar to those for patients aged 65-69 years.
Age Factors ; Aged ; Biopsy ; Disease-Free Survival ; Humans ; Hypertension/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/mortality/pathology/*surgery ; Republic of Korea ; Retrospective Studies

PURPOSE: We investigated the etiologies of lower urinary tract symptoms (LUTS) and compared urodynamic characteristics between different diagnostic groups in young men with chronic LUTS. MATERIALS AND METHODS: We reviewed the medical records of 308 men aged 18 to 50 years who had undergone a urodynamic study for chronic LUTS (> or =6 months) without symptoms suggestive of chronic prostatitis. RESULTS: The men's mean age was 40.4 (+/-10.1) years and their mean duration of symptoms was 38.8 (+/-49.2) months. Urodynamic evaluation demonstrated voiding phase dysfunction in 62.1% of cases (primary bladder neck dysfunction [PBND] in 26.0%, dysfunctional voiding [DV] in 23.4%, and detrusor underactivity [DU]/acontractile detrusor [AD] in 12.7%) and a single storage phase dysfunction in 36.4% of cases (detrusor overactivity [DO] in 13.3%, small cystometric capacity in 17.9%, and reduced bladder sensation in 5.2%). Most of the demographic characteristics and clinical symptoms did not differ between these diagnostic groups. Whereas 53.9% of patients with voiding dysfunction had concomitant storage dysfunction, 69.6% of those with storage dysfunction had concomitant voiding dysfunction. Men with DV or DU/AD exhibited lower maximum cystometric capacity than did those with normal urodynamics. Low bladder compliance was most frequent among patients with PBND (10.0%, p=0.025). In storage dysfunctions, men with DO exhibited higher detrusor pressure during voiding than did those with other storage dysfunctions (p<0.01). CONCLUSIONS: Because clinical symptoms are not useful for predicting the specific urodynamic etiology of LUTS in this population, urodynamic investigation can help to make an accurate diagnosis and, potentially, to guide appropriate treatment.
Compliance ; Diagnosis ; Humans ; Lower Urinary Tract Symptoms* ; Male ; Medical Records ; Neck ; Prevalence ; Prostatitis* ; Sensation ; Urinary Bladder ; Urinary Bladder Diseases ; Urodynamics*

PURPOSE: Among patients over 50 years of age, separate vertical wiring alone may be insufficient for fixation of fractures of the inferior pole of the patella. Therefore, mechanical and clinical studies were performed in patients over the age of 50 to test the strength of augmentation of separate vertical wiring with cerclage wire (i.e., combined technique). MATERIALS AND METHODS: Multiple osteotomies were performed to create four-part fractures in the inferior poles of eight pairs of cadaveric patellae. One patella from each pair was fixed with the separate wiring technique, while the other patella was fixed with a combined technique. The ultimate load to failure and stiffness of the fixation were subsequently measured. In a clinical study of 21 patients (average age of 64 years), comminuted fractures of the inferior pole of the patellae were treated using the combined technique. Operative parameters were recorded from which post-operative outcomes were evaluated. RESULTS: For cadaveric patellae, whose mean age was 69 years, the mean ultimate loads to failure for the separate vertical wiring technique and the combined technique were 216.4+/-72.4 N and 324.9+/-50.6 N, respectively (p=0.012). The mean stiffness for the separate vertical wiring technique and the combined technique was 241.1+/-68.5 N/mm and 340.8+/-45.3 N/mm, respectively (p=0.012). In the clinical study, the mean clinical score at final follow-up was 28.1 points. CONCLUSION: Augmentation of separate vertical wiring with cerclage wire provides enough strength for protected early exercise of the knee joint and uneventful healing.
Aged ; Aged, 80 and over ; *Bone Wires ; Female ; Fracture Fixation, Internal/methods ; Fractures, Comminuted/*surgery ; Humans ; Male ; Middle Aged ; Osteotomy ; Patella/*injuries/*surgery

A 44-year-old male patient who had undergone augmentation penoplasty 20 years previously presented with a slowly growing penoscrotal mass. The penile mass was excised totally and the pathologic diagnosis was an epidermal cyst. Epidermal cysts are benign disorders that can occur in any part of the body. However, an epidermal cyst as a late complication of augmentation penoplasty is extremely rare. We report this case of a penile epidermal cyst that developed after augmentation penoplasty.
Epidermal Cyst ; Humans ; Male ; Penis

BACKGROUND/AIMS: Patients undergoing Billroth II (B II) gastrectomy are at higher risk of perforation during endoscopic retrograde cholangiopancreatography (ERCP). We assessed the success rate and safety of forward-viewing endoscopic biliary intervention in patients with B II gastrectomy. METHODS: A total of 2,280 ERCP procedures were performed in our institution between October 2008 and June 2011. Of these, forward-viewing endoscopic biliary intervention was performed in 46 patients (38 men and 8 women with B II gastrectomy). Wire-guided selective cannulations of the common bile duct using a standard catheter and guide wire were performed in all patients. RESULTS: The success rate of afferent loop entrance was 42 out of 46 patients (91.3%) and of biliary cannulation after the approach of the papilla was 42 out of 42 patients (100%). No serious complications were encountered, except for one case of small perforation due to endoscopic sphincterotomy site injury. CONCLUSIONS: When a biliary endoscopist has less experience and patient volume is low, ERCP with a forward-viewing endoscope is preferred because of its ease and safety in all patients with prior B II gastrectomies. Also, forward-viewing endoscope can be used to improve the success rate of biliary intervention in B II patients.
Catheterization ; Catheters ; Cholangiopancreatography, Endoscopic Retrograde ; Common Bile Duct ; Endoscopes ; Female ; Gastrectomy ; Gastroenterostomy ; Humans ; Male ; Sphincterotomy, Endoscopic