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1.  Growth Inhibition After Exposure to Transforming Growth Factor-β1 in Human Bladder Cancer Cell Lines 
Korean Journal of Urology  2014;55(7):487-492.
Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells.
Materials and Methods
The role of TGF-β1 in bladder cancer cells was examined by observing cell viability by using the tetrazolium dye (MTT) assay after treating the bladder cancer cell lines 253J, 5637, T24, J82, HT1197, and HT1376 with TGF-β1. Among these cell lines, the 253J and T24 cell lines were coincubated with TGF-β1 and the pan anti-TGF-β antibody. Fluorescence-activated cell sorter (FACS) analysis was performed to determine the mechanism involved after TGF-β1 treatment in 253J cells.
All six cell lines showed inhibited cellular growth after TGF-β1 treatment. Although the T24 and J82 cell lines also showed inhibited cellular growth, the growth inhibition was less than that observed in the other 4 cell lines. The addition of pan anti-TGF-β antibodies to the culture media restored the growth properties that had been inhibited by TGF-β1. FACS analysis was performed in the 253J cells and the 253J cells with TGF-β1. There were no significant differences in the cell cycle between the two treatments. However, there were more apoptotic cells in the TGF-β1-treated 253J cells.
TGF-β1 did not stimulate cellular proliferation but was a growth inhibitory factor in bladder cancer cells. However, the pattern of its effects depended on the cell line. TGF-β1 achieved growth inhibition by enhancing the level of apoptosis.
PMCID: PMC4101120  PMID: 25045449
Cell line; Cell survival; Transforming growth factor beta; Urinary bladder neoplasms
2.  Chronic Lower Urinary Tract Symptoms in Young Men Without Symptoms of Chronic Prostatitis: Urodynamic Analyses in 308 Men Aged 50 Years or Younger 
Korean Journal of Urology  2014;55(5):341-348.
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 (≥6 months) without symptoms suggestive of chronic prostatitis.
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).
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.
PMCID: PMC4026661  PMID: 24868339
Age groups; Men; Prevalence; Urinary bladder disease; Urodynamics
3.  Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy 
Prostate International  2014;2(1):26-30.
To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx).
From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV]≥1.0 ng/mL/yr, n=123), and group 3 (PSA fluctuation with PSAV<1.0 ng/mL/yr, n=200).
Prostate cancer was detected in 112 of 492 patients (22.8%) in the repeat biopsy set. According to the PSA fluctuation pattern, prostate cancer detection rates at repeat TRUS-Bx were 29.6% (50/169) for patients with continuously increasing PSA, 30.1% (37/123) for PSA fluctuation with PSAV ≥1.0 ng/mL/yr, and 12.5% (25/200) for PSA fluctuation with PSAV <1.0 ng/mL/yr. Multivariate analysis showed that PSA fluctuation pattern and high grade prostatic intraepithelial neoplasia at initial TRUS-Bx were the predictive parameters for positive repeat biopsies. Among the 96 patients (85.7%) who underwent radical prostatectomy, no significant differences in pathologic outcomes were found according to the PSA fluctuation pattern.
The current study shows that the risk of prostate cancer at repeat TRUS-Bx was higher in men with a fluctuating PSA level and PSAV≥1.0 ng/mL/yr than in those with a fluctuating PSA level and PSAV<1.0 ng/mL/yr.
PMCID: PMC3970986  PMID: 24693531
Prostate-specific antigen; Prostatic neoplasms; Biopsy; Needles
4.  Acute Modulations in Stratum Corneum Permeability Barrier Function Affect Claudin Expression and Epidermal Tight Junction Function via Changes of Epidermal Calcium Gradient 
Yonsei Medical Journal  2013;54(2):523-528.
Tight junction (TJ) is recognized as a second barrier of the skin. Altered expression of TJ proteins in various skin diseases characterized by the abnormal permeability barrier such as psoriasis suggests that TJ could be affected by stratum corneum (SC) barrier status. However, the physiological relationship between SC and TJ barrier remains to be investigated. Therefore, we examined the effect of SC barrier disruption on the expression of TJ proteins, claudin (Cldn)-1 and Cldn-4, and TJ barrier function in hairless mouse skin. We also investigated whether the alterations in epidermal Ca2+ affected TJ proteins expression in vivo. Repeated tape-stripping induced a sequential change of the expression and function of TJ. As early as 15-30 minutes after tape-stripping, downregulation of Cldn-1 and Cldn-4 immunoreactivity and protein level without change in mRNA level was found. This was accompanied by the abnormal leakage of lanthanum. However, by 1 hour Cldn-1 and Cldn-4 immunolocalization recovered along with normalized lanthanum permeation pattern. Moreover, the mRNA and protein levels of Cldn-1 and Cldn-4 were increased by 1 to 6 hours after tape-stripping. Inhibition of calcium loss by immersion of barrier-disrupted skin into a high Ca2+ solution prevented the dislocation of Cldn-1 and Cldn-4. Occlusion of barrier-disrupted skin delayed the restoration of Cldn-1 and Cldn-4. Our results suggest that the alteration of epidermal Ca2+ gradient caused by SC barrier perturbation affects the TJ structure and function and the faster recovery of TJ as compared to the SC barrier may imply the protective homeostatic mechanism of skin barrier.
PMCID: PMC3575975  PMID: 23364991
Tight junction; claudin-1; claudin-4; calcium gradient; stratum corneum permeability barrier
5.  A comprehensive review of neuroanatomy of the prostate 
Prostate International  2013;1(4):139-145.
Although oncologic efficacy is the primary goal of radical prostatectomy, preserving potency and continence is also important, given the indolent clinical course of most prostate cancers. In order to preserve and recover postoperative potency and continence after radical prostatectomy, a detailed understanding of the pelvic anatomy is necessary to recognize the optimal nerve-sparing plane and to minimize injury to the neurovascular bundles. Therefore, we reviewed the most recent findings from neuroanatomic studies of the prostate and adjacent tissues, some of which are contrary to the established consensus on pelvic anatomy. We also described the functional outcomes of radical prostatectomies following improved anatomical understanding and development of surgical techniques for preserving the neurovascular bundles.
PMCID: PMC3879050  PMID: 24392437
Prostatic neoplasms; Neurovascular bundle; Fascial anatomy; Penile erection; Urinary incontinence
6.  Prevalence and Clinical Features of Detrusor Underactivity among Elderly with Lower Urinary Tract Symptoms: A Comparison between Men and Women 
Korean Journal of Urology  2012;53(5):342-348.
To identify the prevalence and clinical features of detrusor underactivity (DU) in elderly men and women presenting with lower urinary tract symptoms (LUTS).
Materials and Methods
We reviewed 1,179 patients aged over 65 years who had undergone a urodynamic study for LUTS with no neurological or anatomical conditions. DU was defined as a bladder contractility index <100 and a maximal flow rate (Qmax) ≤12 ml/s combined with a detrusor pressure at Qmax ≤10 cmH2O for men and women, respectively.
Of the patients, 40.2% of men and 13.3% of women were classified as having DU (p<0.001). Types of clinical symptoms were not significantly different between patients with and without DU. In men, whereas the prevalence of bladder outlet obstruction (BOO) was constant across the age spectrum, the prevalence of DU and detrusor overactivity (DO) increased with age, and 46.5% of men with DU also had DO or BOO. In women, the prevalence of DU also increased with age, and the trend was more remarkable in women aged over 70 years. DU was accompanied by DO or urodynamic stress urinary incontinence (USUI) in 72.6% of the women with DU. Women with DU were found to have lower cystometric capacity and exhibited a greater incidence of reduced compliance than did women without DU.
DU was a common mechanism underlying LUTS in the elderly population, especially in men. One half of the men and three quarters of the women with DU also had other pathologies such as DO, BOO, or USUI.
PMCID: PMC3364474  PMID: 22670194
Aged; Prevalence; Urinary bladder; Urination disorders; Urodynamics
7.  RSC Facilitates Rad59-Dependent Homologous Recombination between Sister Chromatids by Promoting Cohesin Loading at DNA Double-Strand Breaks ▿  
Molecular and Cellular Biology  2011;31(19):3924-3937.
Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.
PMCID: PMC3187356  PMID: 21807899
8.  Sunitinib Malate Synergistically Potentiates Anti-Tumor Effect of Gemcitabine in Human Bladder Cancer Cells 
Korean Journal of Urology  2011;52(1):55-63.
Sunitinib malate (Sutent; Pfizer, New York, NY, USA) is a highly selective multi-targeted agent and has been reported to have potent anti-tumor effects against various tumors, including renal cell carcinoma and gastrointestinal stromal tumors. In this study, we explored in vitro the anti-tumor effect and related molecular mechanisms of sunitinib malate against human bladder cancer cell lines. We also determined the synergistic anti-tumor effect between sunitinib and conventional cytotoxic drugs, cisplatin and gemcitabine, in bladder cancer cells.
Materials and Methods
Six human cancer cell lines (HTB5, HTB9, T24, UMUC14, SW1710, and J82) were exposed to an escalating dose of sunitinib alone or in combination with cisplatin/gemcitabine, and the cytotoxic effect of the drugs was examined by CCK-8 assay. The synergistic effect between sunitinib and cisplatin/gemcitabine was determined by the combination index (CI) and clonogenic assay. Alterations in cell cycle (cyclin D, B1), survival (p-Akt, t-Akt), and apoptosis (Bax, Bad) regulator expression were analyzed by Western blotting.
Like cisplatin and gemcitabine, sunitinib exerted a dose- and time-dependent anti-tumor effect in bladder cancer cells. However, sunitinib exhibited entirely different sensitivity profiles from cisplatin and gemcitabine. Sunitinib suppressed the expression of cyclin B1, p-Akt, and t-Akt while augmenting the expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of the drug combination by the isobolic method and clonogenic assay revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells.
These results indicate that sunitinib malate has a potent anti-tumor effect and may synergistically enhance the anti-tumor effect of gemcitabine in human bladder cancer cells.
PMCID: PMC3037508  PMID: 21344032
Carcinoma; Cisplatin; Gemcitabine; Sunitinib; Urinary bladder
9.  Pre- and Post-Operative Nomograms to Predict Recurrence-Free Probability in Korean Men with Clinically Localized Prostate Cancer 
PLoS ONE  2014;9(6):e100053.
Although the incidence of prostate cancer (PCa) is rapidly increasing in Korea, there are few suitable prediction models for disease recurrence after radical prostatectomy (RP). We established pre- and post-operative nomograms estimating biochemical recurrence (BCR)-free probability after RP in Korean men with clinically localized PCa.
Patients and Methods
Our sampling frame included 3,034 consecutive men with clinically localized PCa who underwent RP at our tertiary centers from June 2004 through July 2011. After inappropriate data exclusion, we evaluated 2,867 patients for the development of nomograms. The Cox proportional hazards regression model was used to develop pre- and post-operative nomograms that predict BCR-free probability. Finally, we resampled from our study cohort 200 times to determine the accuracy of our nomograms on internal validation, which were designated with concordance index (c-index) and further represented by calibration plots.
Over a median of 47 months of follow-up, the estimated BCR-free rate was 87.8% (1 year), 83.8% (2 year), and 72.5% (5 year). In the pre-operative model, Prostate-Specific Antigen (PSA), the proportion of positive biopsy cores, clinical T3a and biopsy Gleason score (GS) were independent predictive factors for BCR, while all relevant predictive factors (PSA, extra-prostatic extension, seminal vesicle invasion, lymph node metastasis, surgical margin, and pathologic GS) were associated with BCR in the post-operative model. The c-index representing predictive accuracy was 0.792 (pre-) and 0.821 (post-operative), showing good fit in the calibration plots.
In summary, we developed pre- and post-operative nomograms predicting BCR-free probability after RP in a large Korean cohort with clinically localized PCa. These nomograms will be provided as the mobile application-based SNUH Prostate Cancer Calculator. Our nomograms can determine patients at high risk of disease recurrence after RP who will benefit from adjuvant therapy.
PMCID: PMC4061043  PMID: 24936784
10.  Regulation of Repair Choice 
DNA repair  2009;8(10):1235-1241.
Cell cycle plays a crucial role in regulating the pathway used to repair DNA double-strand breaks (DSBs). In Saccharomyces cerevisiae, homologous recombination is primarily limited to non-G1 cells as the formation of recombinogenic single-stranded DNA requires CDK1-dependent 5′ to 3′ resection of DNA ends. However, the effect of cell cycle on non-homologous end joining (NHEJ) is not yet clearly defined. Using an assay to quantitatively measure the contributions of each repair pathway to repair product formation and cellular survival after DSB induction, we found that NHEJ is most efficient at G1, and markedly repressed at G2. Repression of NHEJ at G2 is achieved by efficient end resection and by the reduced association of core NHEJ proteins with DNA breaks, both of which depend on the CDK1 activity. Importantly, repression of 5′ end resection by CDK1 inhibition at G2 alone did not fully restore either physical association of Ku/Dnl4-Lif1 with DSBs or NHEJ proficiency to the level at G1. Expression of excess Ku can partially offset the inhibition of end joining at G2. The results suggest that regulation of Ku/Dnl4-Lif1 affinity for DNA ends may contribute to the cell cycle-dependent modulation of NHEJ efficiency.
PMCID: PMC2748135  PMID: 19699692
Double strand break; End joining; Repair choice; Cell cycle
11.  The effect of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy 
The administration of a single dose of propofol is reported to be effective in decreasing the incidence and severity of emergence agitation (EA) in children following sevoflurane anesthesia. The aim of this study was to investigate the clinical usefulness of a single dose of propofol 1 mg/kg at the end of adenotonsillectomy for reducing the incidence of EA after sevoflurane anesthesia.
Ninety children, aged 3-8 years, undergoing adenotonsillectomy were randomized into two groups: the propofol group (n = 45) and the saline group (n = 45), of which 88 children completed the study. Anesthesia was maintained with sevoflurane 2-2.5 vol% and nitrous oxide/oxygen (50%/50%). At the completion of adenotonsillectomy, the propofol group patients were given 1 mg/kg of propofol and the saline group patients were given saline 0.1 ml/kg in the same volume. The incidence of EA was assessed with Aono's four point scale and the severity of EA was assessed with pediatric anesthesia emergence delirium (PAED) scale at 5 min (T5), 15 min (T15) and 30 min (T30) after emergence.
Of the 88 patients, the incidence of EA at T5, T15 and T30 was 61.4%, 27.3%, and 4.5% in the propofol group while in the saline group was 68.2%, 29.5%, and 9.1%, respectively. The incidence and severity of EA were not found to be significantly different between the two groups, but the scales in each group decreased significantly over time.
The administration of propofol 1 mg/kg at the end of surgery did not have any significant effect in reducing the incidence and severity of EA in children undergoing adenotonsillectomy under sevoflurane anesthesia.
PMCID: PMC2926433  PMID: 20740210
Child; Emergence agitation; Propofol; Sevoflurane
12.  Microarray-based genetic screen defines SAW1, a new gene required for Rad1/Rad10-dependent processing of recombination intermediates 
Molecular cell  2008;30(3):325-335.
Elimination of a DSB flanked by direct repeat sequences is mediated by single strand annealing (SSA), which relies on a distinct set of gene products involving recombination, mismatch repair and nucleotide excision repair. Here, we screened for yeast mutants defective in SSA using a plasmid based SSA assay coupled to a bar-code microarray readout. The screen identified Yal027Wp/Saw1 (single-strand annealing weakened 1) and Slx4 besides other known SSA proteins. Saw1 interacts physically with Rad1/Rad10, Msh2/Msh3, and Rad52 proteins and cells lacking SLX4 or SAW1 accumulate recombination intermediates blocked at the Rad1/Rad10-dependent 3’-flap cleavage step. Slx4 and Saw1 also contribute to integrity of ribosomal DNA arrays. Saw1 mutants that fail to interact with Rad1, but retain interaction with Rad52 and Msh2 are defective in 3’-flap removal and SSA repair. Deletion of SAW1 abolished association of Rad1 at SSA intermediates in vivo. We propose that Saw1 targets Rad1/Rad10 to Rad52-coated recombination intermediates.
PMCID: PMC2398651  PMID: 18471978
13.  Leptin, adiponectin and serotonin levels in lean and obese dogs 
BMC Veterinary Research  2014;10:113.
Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors.
Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05).
5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity.
PMCID: PMC4030042  PMID: 24886049
Adiponectin; Leptin; Obese dog; Serotonin
14.  Hand-Assisted Retroperitoneoscopic Nephroureterectomy without Hand-assisted Device 
Journal of Korean Medical Science  2005;20(5):901-903.
Various laparoscopic nephroureterectomy techniques for urothelial carcinoma of the upper urinary tract have been developed to minimize postoperative discomfort and the necessity for a lengthy convalescence. We performed hand-assisted retroperitoneoscopic nephroureterectomy without hand-assisted device in 3 male patients with urothelial carcinoma of the distal ureter. Average operative time and estimated blood loss were 251 min (range 235 to 280) and 250 mL (range 200 to 300), respectively. Complication did not occur and conversion to open surgery was not necessary in all cases. Postoperative analgesic requirements were moderate and the time to regular diet intake averaged 3 days (range 2 to 4). None of the patients had a positive margin on the final pathologic specimen. At the average follow-up of 8.1 months, no regional recurrence, port-site metastasis, bladder recurrence, or distant metastasis were noted in any patient. We described our initial experience with the described technique, which obviates the need for midprocedural patient repositioning.
PMCID: PMC2779296  PMID: 16224173
Ureteral Neoplasms; Retroperitoneal Space; Laparoscopy
15.  Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association 
Nucleic Acids Research  2014;42(10):6393-6404.
The Saccharomyces cerevisiae Rad1-Rad10 complex is a conserved, structure-specific endonuclease important for repairing multiple types of DNA lesions. Upon recruitment to lesion sites, Rad1-Rad10 removes damaged sequences, enabling subsequent gap filling and ligation. Acting at mid-steps of repair, the association and dissociation of Rad1-Rad10 with DNA can influence repair efficiency. We show that genotoxin-enhanced Rad1 sumoylation occurs after the nuclease is recruited to lesion sites. A single lysine outside Rad1's nuclease and Rad10-binding domains is sumoylated in vivo and in vitro. Mutation of this site to arginine abolishes Rad1 sumoylation and impairs Rad1-mediated repair at high doses of DNA damage, but sustains the repair of a single double-stranded break. The timing of Rad1 sumoylation and the phenotype bias toward high lesion loads point to a post-incision role for sumoylation, possibly affecting Rad1 dissociation from DNA. Indeed, biochemical examination shows that sumoylation of Rad1 decreases the complex's affinity for DNA without affecting other protein properties. These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions.
PMCID: PMC4041466  PMID: 24753409
16.  Comparison of 30 mg and 40 mg of Mitomycin C Intravesical Instillation in Korean Superficial Bladder Cancer Patients: Prospective, Randomized Study 
A prospective study was performed to compare the efficacy and safety of intravesical mitomycin C (MMC) instillation for the prophylaxis of bladder cancer at different concentrations (30 mg or 40 mg).
Materials and Methods
Ninety-seven patients that received complete transurethral resection for superficial bladder cancer were divided into two-randomized groups. One group (n=53) received 30 mg and the other group (n=44) received 40 mg dose of MMC weekly for 8 weeks, which was followed monthly for 10 months as maintenance therapy. The recurrence rates and side effects in both groups were recorded. The mean follow-up period was 32.4 months in the 30 mg group, and 32.0 months in the 40 mg group.
The overall one and two year recurrence rates were 19% and 24% in the 30 mg group, and 12% and 22% in the 40 mg group, which was not significantly different (p>0.05). Most of the side effects were mild and transient. Moreover, the rates of the individual side effects were not statistically different in the two groups.
Our comparison of 30 mg and 40 mg intravesical MMC instillation showed no difference in either response or side effects. Thus, we tentatively conclude that we can use 30 mg instead of 40 mg as an intravesical MMC instillation dose.
PMCID: PMC2785421  PMID: 19956509
Bladder neoplasms; Mitomycin C; Instillation therapy
17.  Mobile Application-Based Seoul National University Prostate Cancer Risk Calculator: Development, Validation, and Comparative Analysis with Two Western Risk Calculators in Korean Men 
PLoS ONE  2014;9(4):e94441.
We developed a mobile application-based Seoul National University Prostate Cancer Risk Calculator (SNUPC-RC) that predicts the probability of prostate cancer (PC) at the initial prostate biopsy in a Korean cohort. Additionally, the application was validated and subjected to head-to-head comparisons with internet-based Western risk calculators in a validation cohort. Here, we describe its development and validation.
Patients and Methods
As a retrospective study, consecutive men who underwent initial prostate biopsy with more than 12 cores at a tertiary center were included. In the development stage, 3,482 cases from May 2003 through November 2010 were analyzed. Clinical variables were evaluated, and the final prediction model was developed using the logistic regression model. In the validation stage, 1,112 cases from December 2010 through June 2012 were used. SNUPC-RC was compared with the European Randomized Study of Screening for PC Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC). The clinical value was evaluated using decision curve analysis.
PC was diagnosed in 1,240 (35.6%) and 417 (37.5%) men in the development and validation cohorts, respectively. Age, prostate-specific antigen level, prostate size, and abnormality on digital rectal examination or transrectal ultrasonography were significant factors of PC and were included in the final model. The predictive accuracy in the development cohort was 0.786. In the validation cohort, AUC was significantly higher for the SNUPC-RC (0.811) than for ERSPC-RC (0.768, p<0.001) and PCPT-RC (0.704, p<0.001). Decision curve analysis also showed higher net benefits with SNUPC-RC than with the other calculators.
SNUPC-RC has a higher predictive accuracy and clinical benefit than Western risk calculators. Furthermore, it is easy to use because it is available as a mobile application for smart devices.
PMCID: PMC3978062  PMID: 24710020
18.  The Nephrometry Score: Is It Effective for Predicting Perioperative Outcome During Robot-Assisted Partial Nephrectomy? 
Korean Journal of Urology  2014;55(4):254-259.
Robot-assisted partial nephrectomy (RPN) has emerged as an alternative treatment for the management of small renal masses. This study was designed to investigate parameters that predict perioperative outcomes during RPN.
Materials and Methods
We retrospectively reviewed the medical records of 113 patients who underwent RPN between September 2008 and May 2012 at the Seoul National University Bundang Hospital. Clinical parameters, including warm ischemia time (WIT), estimated blood loss (EBL), and R.E.N.A.L and PADUA scores, were evaluated to predict perioperative outcomes.
Of the 113 patients, 81 were men and 32 were women. The patients' mean age was 53.5 years, and their mean body mass index was 22.3 kg/m2. Age, gender, and mass laterality had no effect on perioperative complications, WIT, or EBL. Univariate analysis revealed that a distance between the tumor and the collecting system of ≤4 mm or a renal mass size of >4 cm were associated with adverse profiles of complications, WIT, and EBL. However, multivariate analysis showed no association between the predictive parameters and tumor complexity as assessed by nephrometry scores. Tumor size of >4 cm increased the risk of blood loss >300 mL (odds ratio [OR], 3.5; 95% confidence interval [CI],; p=0.016). A distance between the tumor and the collecting system of ≤4 mm was associated with increased risk of WIT exceeding 20 minutes (OR, 2.8; 95% CI,; p=0.012).
Tumor size and proximity of the mass to the collecting system showed significant associations with EBL and WIT, respectively, during RPN. The R.E.N.A.L and PADUA nephrometry scoring systems did not predict perioperative outcomes.
PMCID: PMC3988436  PMID: 24741414
Nephrectomy; Renal cell carcinoma; Robotics; Surgical blood loss; Warm ischemia
19.  Combination of clinical characteristics and transrectal ultrasound-guided biopsy to predict lobes without significant cancer: application in patient selection for hemiablative focal therapy 
Prostate International  2014;2(1):37-42.
A major limitation of performing hemiablative focal therapy (FT) for prostate cancer (PCa) is the possibility of accompanying significant cancer in the contralateral side of the prostate that is missed on prostate biopsy. We attempted to verify whether clinical and biopsy-related parameters can be used to predict the absence of significant cancer in the prostate lobe.
We assumed that hemiablative FT could be performed in patients with low-risk PCa, with unilateral tumors as assessed by transrectal ultrasound-guided biopsy. We evaluated 214 patients who had undergone radical prostatectomy (RP) and fulfilled the eligibility criteria. Seemingly preserved lobes, defined by the absence of cancer on biopsy, were classified as lobes with no cancer (LNC), lobes with insignificant cancer (LIC), and lobes with significant cancer (LSC) according to RP pathology. Cases with an estimated tumor volume of <0.5 mL, a Gleason score of <7, and organ confinement without Gleason pattern 4 were classified as LIC. Univariate and multivariate logistic regression analyses were performed to identify predictors for LSC. Predictive accuracies of the multivariate models were assessed using receiver operating characteristic curve-derived areas under the curve.
Of 214 evaluated lobes, 45 (21.0%), 62, (29.0%), and 107 (50.0%) were classified as LNC, LIC, and LSC, respectively. Among the clinical and biopsy-related parameters, prostate-specific antigen density and prostate volume were identified as significant predictors for LSC in univariate regression analysis. However, multivariate analysis did not identify an independent predictor. Predictive accuracies of the multivariate models did not exceed 70.4%.
Conventional parameters have limited value in predicting LSC in patients who are candidates for hemiablative FT.
PMCID: PMC3970988  PMID: 24693533
Prostatic neoplasms; Tissue preservation; Patient selection
20.  Comparison of respiratory mechanics between sevoflurane and propofol-remifentanil anesthesia for laparoscopic colectomy 
Korean Journal of Anesthesiology  2014;66(2):131-135.
The creation of pneumoperitoneum and Trendelenburg positioning during laparoscopic surgery are associated with respiratory changes. We aimed to compare respiratory mechanics while using intravenous propofol and remifentanil vs. sevoflurane during laparoscopic colectomy.
Sixty patients undergoing laparoscopic colectomy were randomly allocated to one of the two groups: group PR (propofol-remifentanil group; n = 30), and group S (sevoflurane group; n = 30). Peak inspiratory pressure (PIP), dynamic lung compliance (Cdyn), and respiratory resistance (Rrs) values at five different time points: 5 minutes after induction of anesthesia (supine position, T1), 3 minutes after pneumoperitoneum (lithotomy position, T2), 3 minutes after pneumoperitoneum while in the lithotomy-Trendelenburg position (T3), 30 minutes after pneumoperitoneum (T4), and 3 minutes after deflation of pneumoperitoneum (T5).
In both groups, there were significant increases in PIP and Rrs while Cdyn decreased at times T2, T3, and T4 compared to T1 (P < 0.001). The Rrs of group PR for T2, T3, and T4 were significantly higher than those measured in group S for the corresponding time points (P < 0.05).
Respiratory mechanics can be adversely affected during laparoscopic colectomy. Respiratory resistance was significantly higher during propofol-remifentanil anesthesia than sevoflurane anesthesia.
PMCID: PMC3948440  PMID: 24624271
Laparoscopy; Propofol; Remifentanil; Respiratory mechanics; Sevoflurane
21.  Molecular Characterization of Giardia duodenalis and Cryptosporidium parvum in Fecal Samples of Individuals in Mongolia 
The Giardia and Cryptosporidium species are widespread and frequent diarrhea-related parasites affecting humans and other mammalian species. The prevalence of these parasites in Mongolia is currently unknown. Therefore, we performed molecular analyses of G. duodenalis and C. parvum in stool samples from 138 patients hospitalized with diarrhea in Mongolia using nested polymerase chain reaction (PCR). A total of 5 (3.62%) and 7 (5.07%) fecal samples were positive for G. duodenalis and C. parvum, respectively. Giardia duodenalis and C. parvum infections were prevalent in children < 9 years of age. The assemblage-specific fragment patterns for the β-giardin gene of G. duodenalis revealed that all five samples testing positive belonged to Assemblage A by the PCR-restriction fragment polymorphism method. For sequencing and phylogenetic analysis of the 18S rDNA and HSP70 genes of all seven patients testing positive the genes were further identified to be of the C. parvum bovine genotype. This study is the first to report the prevalence of G. duodenalis and C. parvum and its molecular characterization of fecal samples from individuals with diarrhea in Mongolia.
PMCID: PMC3886425  PMID: 24249428
22.  Prevalence of Toxoplasma gondii Infection in Rabbits of Korea by Serological Tests and Nested Polymerase Chain Reaction 
>This study surveyed the Toxoplasma (T.) gondii infection prevalence in the Korean rabbit population. Rabbits (n=142) were obtained from two breeding farms in the Gongju area, Chungnam Province, and in the Kochang area, Junbuk Province, Korea. Of 142 sera samples analyzed by enzyme-linked immunosorbent assay (ELISA), 15 (10.6%) exhibited T. gondii-specific IgG antibodies, and 1 (0.7%) rabbit harbored T. gondii-specific IgM. Female rabbits (9/84; 10.7%) had a similar T. gondii prevalence to males (6/58; 10.3%). When stratified by age, rabbits aged >1 year had a similar prevalence of T. gondii infection (7/66; 10.6%) to rabbits aged <1 year (8/76; 10.5%). Immunoblotting detected 6 major antigenic bands corresponding to T. gondii-positive sera at 20, 28, 30, 35, 63 and 77 kDa. Nested polymerase chain reaction (PCR) of whole-blood samples detected the T. gondii B1 gene in 23 rabbits (16.2%). All PCR-positive samples corresponded to partial T. gondii B1 gene sequences with 99% homology to a T. gondii sequence deposited in GenBank (accession number EU340874). Female rabbits (13/84; 15.5%) harbored a similar prevalence of T. gondii DNA to males (10/58; 17.2%). Rabbits aged >1 year had a similar prevalence (12/66; 18.2%) of T. gondii infection to rabbits aged <1 year (11/76; 14.5%). No statistically significant differences were observed regarding the prevalences of infection according to sex or age using molecular or serological tests. This study is the first survey using serological tests and nested PCR to analyze the T. gondii prevalence in rabbits in Korea.
PMCID: PMC3942966  PMID: 23955398
ELISA; immunoblotting; nested PCR; rabbit; Toxoplasma gondii
23.  Development of a Rabbit Model for a Preclinical Comparison of Coronary Stent Types In-Vivo 
Korean Circulation Journal  2013;43(11):713-722.
Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.
PMCID: PMC3866309  PMID: 24363745
Prosthesis and implants; Stents; Model, animal; NZW rabbits
24.  Comparison of Continence Recovery Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Single Surgeon Experience 
Korean Journal of Urology  2013;54(9):598-602.
To evaluate the recovery of continence after robot-assisted laparoscopic prostatectomy (RALP) and open radical retropubic prostatectomy (RRP).
Materials and Methods
We identified 258 patients who underwent surgery by a single surgeon to treat localized prostate cancer. The patients were divided into two groups according to operative method. In group 1, 146 consecutive patients underwent RALP, and in group 2, 112 patients underwent RRP. To compare the interval until the return of urinary continence between the two groups, we used the Kaplan-Meier method and the log-rank test and Cox proportional hazard regression analyses.
Differences between the two groups were found in mean estimated blood loss (EBL; p<0.001) and the rate of nerve sparing (p=0.004). When continence was defined as the use of 0 to 1 pad per day, 100% of group 1 and 98.2% of group 2 reported continence at 12 months (p=0.189). When continence was defined as no pad use, however, there was a significant difference between the two groups at 12 months: group 1, 95.7%, and group 2, 70.7% (p<0.001). The factors affecting time until no pad use in the univariate analysis with a Cox proportional hazards model were operation method, age, neurovascular bundle saving, membranous urethral length (MUL), EBL, and apical shape. In the multivariate analysis, only operation method, age, and MUL retained significance.
Our study suggests that RALP is an independent factor for the recovery of continence and that RALP has advantages for postoperative continence recovery and the quality of continence compared with RRP.
PMCID: PMC3773589  PMID: 24044093
Prostate neoplasms; Prostatectomy; Robotics; Urinary incontinence
25.  Rhox in mammalian reproduction and development 
Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, α, β, and γ in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into α (Rhox1-4), β (Rhox5-9), and γ (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells.
PMCID: PMC3811726  PMID: 24179867
Embryonic development; Gametogenesis; Homeobox gene; Reproduction; Rhox; Stem cells

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